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The cross section of the process e^{+}e^{-}âπ^{+}π^{-} has been measured in the center-of-mass energy range from 0.32 to 1.2 GeV with the CMD-3 detector at the electron-positron collider VEPP-2000. The measurement is based on an integrated luminosity of about 88 pb^{-1}, of which 62 pb^{-1} represent a complete dataset collected by CMD-3 at center-of-mass energies below 1 GeV. In the dominant region near the ρ resonance a systematic uncertainty of 0.7% was achieved. The implications of the presented results for the evaluation of the hadronic contribution to the anomalous magnetic moment of the muon are discussed.
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BACKGROUND: Hodgkin lymphoma (HL) in pediatric populations has a high survival rate but poses risks for long-term morbidities. Although [18F]fluoro2deoxy2dglucose positron emission tomography ([18F]FDG PET) scans offer potential for improved risk stratification, the definitive prognostic value of quantitative [18F]FDG PET parameters remains unclear for pediatric HL. METHODS: A single-center, retrospective study included pediatric patients diagnosed with HL between 2016 and 2023 treated according to EuroNet-PHL-C1 and DAL/GPOH-HD protocols. Patients underwent baseline and interim PET/CT scans after two chemotherapy cycles. Event-free survival (EFS) was the primary endpoint, Deauville score was the secondary endpoint. Quantitative [18F]FDG PET parameters included SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) that were evaluated using two segmentation methods (SUV 2.5, 41% SUVmax). Survival outcomes were assessed using Cox regression analysis. RESULTS: A total of 115 patients (50 males, median age 14.2 years) were studied, with a median follow-up period of 35 months. During this period, 16 cases (13.9%) of relapse or progression were noted. Baseline and interim MTV 2.5, MTV 41%, TLG 2.5, and TLG 41%, along with interim SUVmax, were significantly associated with worse EFS and correlated with post-treatment Deauville scores. In multivariable analysis, interim MTV 2.5 > 0 ml (adj. hazard ratio, HR: 3.89, p = 0.009) and interim TLG 41% ≥ 30 g (adj. HR: 7.98, p = 0.006) were independent risk factors for EFS. CONCLUSION: Baseline and interim [18F]FDG PET parameters can serve as significant prognostic indicators for EFS and treatment response in pediatric HL. These quantitative measures could enhance individualized, risk-adapted treatment strategies for children and adolescents with HL.
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Fluordesoxiglucose F18 , Doença de Hodgkin , Humanos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/metabolismo , Masculino , Feminino , Adolescente , Criança , Prognóstico , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pré-EscolarRESUMO
AIM: To assess the predictive value of T2-weighted (T2W) magnetic resonance imaging (MRI) in combination with diffusion-weighted imaging (DWI) for determining the pathological grading of solid lung adenocarcinoma. MATERIALS AND METHODS: The clinical and imaging data from 153 cases of solid lung adenocarcinoma (82 men, 71 women, mean age 63.2 years) confirmed at histopathology in The First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to May 2022 were analysed retrospectively. Adenocarcinomas were classified into low-grade (G1 and G2) and high-grade (G3) groups following the 2020 pathological grading system proposed by the International Association for the Study of Lung Cancer. The T2-weighted contrast ratio (T2CR), calculated as the T2 signal intensity of the lung mass/nodule divided by the T2 signal intensity of the right rhomboid muscle was utilised. Two experienced radiologists reviewed the MRI images independently, measured the T2CR, and obtained apparent diffusion coefficient (ADC) values. The Mann-Whitney U-test was used to compare general characteristics (sex, age, maximum diameter), T2CR, and ADC values between the low-grade and high-grade groups. The non-parametric Kruskal-Wallis test determined differences in T2CR and ADC values among the five adenocarcinoma subtypes. Receiver characteristic curve (ROC) analysis, along with area under the curve (AUC) calculation, assessed the effectiveness of each parameter in distinguishing the pathological grade of lung adenocarcinoma. A Z-test was used to compare the AUC values. RESULTS: Among the 153 patients with adenocarcinoma, 103 had low-grade adenocarcinoma, and 50 had high-grade adenocarcinoma. The agreement between T2CR and ADC observers was good (0.948 and 0.929, respectively). None of the parameters followed a normal distribution (p<0.05). The ADC value was lower in the high-grade adenocarcinoma group compared to the low-grade adenocarcinoma group (p=0.004), while the T2CR value was higher in the high-grade group (p=0.011). Statistically significant differences were observed in maximum diameter and gender between the two groups (p<0.001 and p=0.005, respectively), while no significant differences were noted in age (p=0.980). Among the five adenocarcinoma subtypes, only the lepidic and micropapillary subtypes displayed statistical differences in ADC values (p=0.047), with the remaining subtypes showing no statistical differences (p>0.05). The AUC values for distinguishing high-grade adenocarcinoma from low-grade adenocarcinoma were 0.645 for ADC and 0.627 for T2CR. Combining T2CR, ADC, sex, and maximum diameter resulted in an AUC of 0.778, sensitivity of 70%, and specificity of 75%. This combination significantly improved diagnostic efficiency compared to T2CR and ADC alone (p=0.008, z = 2.624; p=0.007, z = 2.679). CONCLUSION: The MRI quantitative parameters are useful for distinguishing the pathological grades of solid lung adenocarcinoma, offering valuable insights for precise lung cancer treatment.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma de Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagemRESUMO
BACKGROUND: Posterior nasal neurectomy (PNN) is a commonly employed surgical approach for the treatment of allergic rhinitis (AR). Due to its denervation effect on the nasal mucosa, PNN may potentially alter the motion and defensive capability of cilia. Previous research on the effects of neural regulation and denervation on cilia has been limited by the absence of a feasible in vivo evaluation method for assessing ciliary function. METHODOLOGY: Utilizing a new system developed by our team for visualizing and analyzing ciliary motion in vivo, we analysed ciliary beat frequency and distance in vivo and histomorphological changes in a murine PNN and AR model. Ovalbumin, histamine and neurotransmitters (acetylcholine chloride, α receptor agonist and ß receptor agonist) were applied to investigate the responsiveness and neural regulation of the nasal mucosa. RESULTS: Denervation resulting from PNN led to a reduction in nasal ciliary beat frequency (CBF) to 78% of the control, as well as diminished response towards allergens and histamine. Among neurotransmitters examined, α receptor agonists exhibited inhibitory effects on in vivo ciliary motion while acetylcholine and ß receptor agonists demonstrated stimulatory effects. PNN did not affect the reactivity of in vivo cilia towards these neurotransmitters. CONCLUSIONS: PNN-induced denervation can reduce ciliary motion, potentially compromising the defensive capability of nasal mucosa. Neural regulation and the neurotransmitters involved have significant effect on ciliary motion.
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Cílios , Modelos Animais de Doenças , Mucosa Nasal , Rinite Alérgica , Animais , Camundongos , Mucosa Nasal/inervação , Mucosa Nasal/cirurgia , Rinite Alérgica/cirurgia , Denervação/métodos , Camundongos Endogâmicos BALB C , Depuração MucociliarRESUMO
INTRODUCTION: Surgical repair of aortic arch hypoplasia in children requires a "dry" surgical field with reliable end-organ protection. Perfusion strategies commonly involve deep hypothermic circulatory arrest (DHCA) and variations of the continuous perfusion techniques, such as selective antegrade cerebral perfusion (SACP) and full-flow perfusion with double aortic cannulation (DAC). We aimed to evaluate the end-organ protection in the surgery of aortic arch hypoplasia in newborns and infants using DHCA and DAC. MATERIALS AND METHODS: 66 newborns and infants with aortic arch hypoplasia and biventricular anatomy were enrolled in this prospective study. Patients were randomly assigned into two groups according to the perfusion strategy - DHCA (n = 33); and DAC (n = 33). Primary endpoint: acute kidney injury (AKI), graded according to the KDIGO score. Secondary endpoints: neurological sequelae (pre- and postoperative MRI), in-hospital mortality. RESULTS: The lowest temperature was 32 (28; 34)°Ð¡ in the DAC group and 23 (20; 25)°Ð¡ in the DHCA group. The patients with DAC had lower incidence of AKI (6 patients (18.2%) versus 19 patients (57.6%); p = .017). In the multivariate analysis, the inotropic index at 48 h was identified as a risk factor, increasing the risk of AKI by 4%. The DHCA group was associated with a 3.8-fold increase in the risk of AKI. There was no difference in hospital mortality between the DAC and DHCA groups (1 patient (3%) versus 3 patients (9.1%); p = .61). Neurological sequelae by MRI scan were observed in 18 patients (54.5%) in the DHCA group compared to 5 patients (15.15%) in the DAC group (p = .026). The only risk factor identified in the multivariate analysis for neurological lesions on MRI scan was the DHCA group, which increased the risk by 8.8 times. CONCLUSIONS: Surgical reconstruction of the aortic arch hypoplasia using the method of full-body perfusion reduces the incidence of neurological lesions and renal complications requiring renal replacement therapy compared with the deep hypothermic circulatory arrest in neonates and infants.
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The objective of the study was to identify different phenotypes of overweight in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) based on body mass index (BMI) and serum leptin levels, as well as to determine the frequencies of various metabolic disorders, hypertension, and cardiovascular complications (CVCs) in individual phenotypes. The study included 50 women with RA and 46 with SLE aged 18 to 65 years without a history of diabetes and fasting hyperglycemia. In all patients, the concentration of leptin was determined by ELISA, the concentration of insulin was determined by electrochemiluminescence analysis, and the HOMA-IR index was calculated. Hyperleptinemia was diagnosed at leptin concentrations > 11.1 ng/mL; insulin resistance (IR), at HOMA-IR values ≥ 2.77. Three main phenotypes of overweight were distinguished: "classic" (BMI ≥ 25 kg/m2 + hyperleptinemia), "healthy" (BMI ≥ 25 kg/m2, without hyperleptinemia), "hidden" or "latent" (BMI < 25 kg/m2 + hyperleptinemia), as well as "normal weight" (BMI < 25 kg/m2, without hyperleptinemia). Patients with RA and SLE were similar in age (p = 0.4), disease duration (p = 0.2) and BMI (p = 0.5). Hyperleptinemia was found in 46% of women with RA and in 74% of women with SLE (p = 0.005), and IR was found in 10 and 22% of patients, respectively (p = 0.2). The "classic" phenotype of overweight was diagnosed in 30%, "healthy" in 8%, and "hidden" in 16% of cases with RA and in 44%, 0%, and 30% of cases with SLE, respectively. IR was found in 3% and hypertension in 6% of patients with "normal weight." With the "classic" phenotype, IR (29%) and hypertension (66%) were more common than with "normal weight" (p < 0.01 in all cases); with the "hidden" phenotype, significant differences were obtained only in hypertension frequency (45%; p = 0.0012), but not IR (18%). Three out of four women with a history of cardiovascular complications suffered from "classic" overweight, and one patient had a "normal weight." In women with SLE up to 65 years of age, the frequency of hyperleptinemia, but not IR, is higher than in patients with RA. In both diseases, the "classic" overweight phenotype is most common. In RA, a "hidden" phenotype was detected less often than in SLE, at the same time, a "healthy" phenotype is not characteristic of SLE. The frequency of metabolic disorders and hypertension is low with the "normal weight" and "healthy" phenotype, high with the "classic" phenotype, and intermediate with the "hidden" phenotype.
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Artrite Reumatoide , Biomarcadores , Leptina , Lúpus Eritematoso Sistêmico , Obesidade , Sobrepeso , Fenótipo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Feminino , Adulto , Leptina/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Sobrepeso/sangue , Sobrepeso/complicações , Biomarcadores/sangue , Idoso , Índice de Massa Corporal , Adolescente , Adulto JovemRESUMO
. Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here, we present 1-year efficacy and safety data of the SOLAR study. OBJECTIVES: . To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA. MATERIALS AND METHODS: : The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021. Adult subjects (154) aged ≥18 years with confirmed diagnosis of RA1 were randomly assigned (2 : 1) to receive either levilimab (162 mg, SC, QW) + MTX (n = 102) or placebo + MTX (n = 52). After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP > 2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was performed in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases. Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n = 152). RESULTS: : Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%). LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52. The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%), blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%), and injection site reactions (5.9%). No deaths occurred. CONCLUSIONS: : Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to levilimab maintenance regimen (once every 2 weeks) (Q2W) in those who achieved remission of RA at week 24.
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Artrite Reumatoide , Quimioterapia Combinada , Metotrexato , Humanos , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Método Duplo-Cego , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Antirreumáticos/uso terapêutico , Antirreumáticos/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversosRESUMO
The most important component of cardio-oncology is the assessment of the risk of development and diagnosis of cardiovascular toxicity of the antitumor therapy, the detection of which is largely based on visualization of the cardiovascular system. The article addresses up-to-date methods of non-invasive visualization of the heart and blood vessels, according to the 2022 European Society of Cardiology Clinical Guidelines on cardio-oncology. Also, the article discusses promising cardiovascular imaging techniques that are not yet included in the guidelines: assessment of coronary calcium using multislice computed tomography and positron emission computed tomography with 18F-labeled 2-deoxy-2-fluoro-d-glucose.
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Cardiotoxicidade , Humanos , Medição de Risco/métodos , Cardiotoxicidade/etiologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Doenças Cardiovasculares/diagnósticoRESUMO
Significant advances in timely diagnosis and modern antitumor therapy have led to a considerable increase in the survival rate of cancer patients. On the other hand, the incidence of cardiovascular (CV) diseases and their complications is increasingly growing, including due to side effects of anticancer drugs. CV complications are the most common cause of non-oncological death of cancer patients. The development of polychemotherapy-induced arterial hypertension (AH) is closely associated with the use of certain groups of drugs, for example, inhibitors of vascular endothelial growth factor (iVEGF). Such AH is generally dose-dependent and reversible after interruption or termination of treatment. However, systemic AH, regardless of its genesis, is one of the key risk factors for many CV events (myocardial infarction, stroke, heart failure, arrhythmias) and kidney disease. Therefore, thorough blood pressure monitoring and its timely and adequate correction if needed are indicated when using certain groups of chemotherapy drugs. This article describes a clinical follow-up of a patient with induced AH associated with the iVEGF antitumor therapy for advanced uterine cancer with a rapid development of left ventricular myocardial dysfunction.
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Hipertensão , Humanos , Feminino , Hipertensão/induzido quimicamente , Cardiotoxicidade/etiologia , Pessoa de Meia-Idade , Neoplasias Uterinas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
AIM: To discuss two aspects that can be used to improve the adherence to therapy in patients with arterial hypertension (AH): 1) which of the angiotensin II receptor blockers (ARBs) provides the highest adherence rates; 2) how various factors influence adherence rates. MATERIAL AND METHODS: An analysis of one of the world's largest clinical practice databases, Truven Health Analytics MarketScan (currently Merative MarketScan), was performed. The analysis included data on patients of both sexes aged 30 to 65 years who had been diagnosed with uncomplicated AH (at least once between March 1, 2012 and January 1, 2018) and prescribed monotherapy with one of ARBs. The exclusion criteria were heart failure and the treatment with two or more ARBs (simultaneously or sequentially) during the treatment period. Ultimately, the study included 717,099 patients with uncomplicated AH, who were divided into four groups based on the prescribed drug: azilsartan (n=4276), candesartan (n=6023), losartan (n=586,857), and valsartan (n=119,943). Adherence to treatment was evaluated by two parameters: duration of continuous therapy and medication possession ratio (MPR). The individual effect of each factor (specific ARB used for therapy, patient gender, age, initial ARB dose, patient co-payment per day of treatment) on the adherence to treatment was assessed using a regression analysis. RESULTS: The adherence to the ARB therapy was generally high. The MPR was the lowest in the azilsartan group and the highest in the candesartan group. However, the parameters that potentially influenced both the MPR and the duration of continuous therapy (patient's gender and age, initial ARB dose, co-payment size) differed significantly between the groups receiving different ARBs. The regression analysis showed that both adherence parameters and the duration of continuous therapy were higher in patients receiving candesartan than in patients receiving azilsartan, losartan or valsartan, when the effect on the adherence of other factors available for study (age, gender, initial dose of the drug, and the absolute size of co-payment for a day of therapy) was excluded. The lowest adherence to therapy was observed in the azilsartan treatment group (p<0.01). CONCLUSION: The study provided data for comparing the adherence of patients with uncomplicated AH to the therapy with different ARBs. Further study of adherence to treatment will provide additional data that will allow an optimal selection of drugs for the treatment of AH in patients with potentially poor adherence.
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Antagonistas de Receptores de Angiotensina , Hipertensão , Adesão à Medicação , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Hipertensão/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/administração & dosagem , Estados Unidos , Idoso , Bases de Dados Factuais , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagemRESUMO
AIM: To study the long-term effect of enhanced external counterpulsation (EECP) therapy on exercise tolerance, quality of life (QoL), and indicators of the structural and functional state of the cardiovascular system in patients with stable ischemic heart disease (IHD) complicated by chronic heart failure (CHF). MATERIAL AND METHODS: This open randomized EXCEL study included 120 patients with verified IHD complicated by NYHA II-III functional class CHF with reduced or mid-range left ventricular (LV) ejection fraction. Patients were randomized into group 1 (n=40), optimal drug therapy (ODT) and EECP (35 hours, 2 courses per year); group 2 (n=40), ODT and EECP (35 hours, 1 course per year); and group 3 (control; n=40), ODT and placebo counterpulsation (35âh, 1 course per year). All patients underwent a 6-minute walk test (6MWT), evaluation of clinical status, QoL with the MLHFQ and SF-36 questionnaires, structural and functional state of large blood vessels and microvasculature, measurement of brain natriuretic peptide precursor (NT-proBNP), and echocardiography at baseline and after 12 months. RESULTS: In groups 1 and 2 after 12 months, the 6MWT distance increased statistically significantly (44.5 and 24.9%, respectively) and the following indexes improved: QoL (SF-36, MLHFQ), the condition of large blood vessels (phase shift, radial augmentation index, central aortic systolic pressure (CASP)) and microvasculature (occlusion index, percentage of perfused capillaries, percentage of capillary recovery), and the LV systolic function (from 40.6±7.5 to 47.5±10.2% and from 41.3± 6.8 to 43.9±10.3%, respectively). The proportion of patients with a >20% increase in the 6MWT at 12 months was 97.5, 72.5, and 7.7%, respectively. A statistically significant decrease in NT-proBNP was observed in all groups. In group 3, the incidence of hospitalizations for CHF and the risk of the composite endpoint were significantly higher. CONCLUSION: For the 12-month study period, the effects of EECP in patients with IHD complicated by CHF included improvements in exercise tolerance, QoL, vascular and cardiac functional parameters, and a decrease in the incidence of adverse outcomes.
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Insuficiência Cardíaca , Isquemia Miocárdica , Humanos , Qualidade de Vida , Função Ventricular Esquerda , Volume Sistólico , Doença Crônica , Peptídeo Natriurético Encefálico/uso terapêuticoRESUMO
AIM: To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease. MATERIAL AND METHODS: This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis <50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients. RESULTS: The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p<0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p<0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p <0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= -0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23âpg/ml suggests the absence of hemodynamically significant CA stenosis. CONCLUSION: IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.
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Angiografia Coronária , MicroRNAs , Fator A de Crescimento do Endotélio Vascular , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Fator A de Crescimento do Endotélio Vascular/genética , MicroRNAs/genética , Estudos Transversais , Idoso , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico , Metaloproteinases da Matriz/genética , Biomarcadores , Estenose Coronária/genética , Estenose Coronária/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologiaRESUMO
AIM: To evaluate the dynamics of specific biomarkers for cardiotoxicity, endothelial dysfunction, fibrosis, systemic inflammation, and morpho-functional alterations in the left ventricular (LV) myocardium in patients with newly diagnosed lymphomas during 6 courses of polychemotherapy (PCT). MATERIAL AND METHODS: The study included 30 patients with newly diagnosed lymphomas. All patients were evaluated for laboratory markers of cardiotoxicity at baseline and after 6 courses of chemotherapy (6 months), including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), endothelin-1 (ET-1), circulating cardiac biomarker ST-2, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and LV structural and functional echocardiographic (EchoCG) parameters. RESULTS: The changes in NT-proBNP and hsTnI concentrations during 6 courses of PCT were not statistically significant. Comparison of the baseline values with those after 6 courses of PCT showed increases in the median concentrations of ET-1 (3.38 and 5.5 pg/ml, respectively; p=0.438) and ST-2 (12.21 and 26.75 ng/ml, respectively; p=0.687). Markers of systemic inflammation were significantly decreased after 6 courses of PCT: the median CRP decreased from 15.2 to 0.72 mg/ml (p=0.006), and the median IL-6 decreased from 12.2 to 5.1 pg/ml (p=0.034). EchoCG data revealed a statistically significant impairment of the LV diastolic function parameters (E/A; E/e' lateral; E/e' average; left atrial volume index; isovolumic relaxation time). A moderate direct correlation was found between the ET-1 concentration and the isovolumic relaxation time at baseline and after 6 courses of PCT, respectively (r1 = 0.387, p=0.047 and r2 = 0.391, p=0.035). No changes in the LV systolic function were observed. CONCLUSION: The study showed that patients with lymphoproliferative diseases had no signs of cardiotoxicity during PCT according to the accepted criteria. This study described and highlighted for the first time the interrelation of endothelial dysfunction, profibrotic status, and LV diastolic dysfunction as manifestations of cardiovascular toxicity in patients with lymphoproliferative diseases. It is advisable to supplement the integrated strategies for the prevention and monitoring of PCT cardiovascular toxicity with a thorough evaluation of instrumental parameters of diastolic dysfunction for timely initiation/correction of cardioprotective therapy.
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Biomarcadores , Ecocardiografia , Ventrículos do Coração , Linfoma , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Linfoma/tratamento farmacológico , Linfoma/fisiopatologia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ecocardiografia/métodos , Endotelina-1/sangue , Adulto , Cardiotoxicidade/etiologia , Peptídeo Natriurético Encefálico/sangue , Troponina I/sangue , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico , Proteína C-Reativa/análise , Fragmentos de Peptídeos/sangue , Função Ventricular Esquerda/fisiologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
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
AIM: Assessment of WNT1, WNT3a, and LRP6 concentrations in patients with ischemic heart disease (IHD) and obstructive and non-obstructive coronary artery (CA) disease. MATERIAL AND METHODS: This cross-sectional observational study included 50 IHD patients (verified by coronary angiography, CAG), of which 25 (50%) were men, mean age 64.9±8.1 years; 20 patients had non-obstructive CA disease (stenosis <50%), and 30 patients had hemodynamically significant stenosis. Concentrations of WNT1, WNT3a and LRP6 were measured in all patients. RESULTS: The concentrations of WNT1 and WNT3a proteins were significantly higher in patients with IHD and obstructive CA disease (p < 0.001), while the concentration of LRP6 was higher in the group with non-obstructive CA disease (p = 0.016). Data analysis of the group with obstructive CA disease showed a moderate correlation between WNT1 and LRP6 (ρ=0.374; p=0.042). Correlation analysis of all groups of patients with CA disease revealed a moderate association between the concentrations of WNT1 and uric acid (ρ=0.416; p=0.007). Regression analysis showed that risk factors for the development of IHD, such as increased body mass index, age, smoking, dyslipidemia, and hypertension, did not significantly influence the type of CA disease in IHD patients. According to ROC analysis, the obstructive form of IHD was predicted by a WNT3a concentration higher than 0.155 ng/ml and a LRP6 concentration lower than 12.94 ng/ml. CONCLUSION: IHD patients with non-obstructive CA disease had the greatest increase in LRP6, while patients with obstructive CA disease had significantly higher concentrations of the canonical WNT cascade proteins, WNT1 and WNT3a. According to the ROC analysis, a WNT3a concentration >0.155 ng/ml can serve as a predictor for the presence of hemodynamically significant CA stenosis in IHD patients (sensitivity 96.7%; specificity 70%), whereas a LRP6 concentration >12.94 ng/ml can predict the development of non-obstructive CA disease (sensitivity 76.7%; specificity 65%).
Assuntos
Doença da Artéria Coronariana , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Via de Sinalização Wnt , Humanos , Masculino , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/fisiopatologia , Estudos Transversais , Idoso , Via de Sinalização Wnt/fisiologia , Proteína Wnt3A/metabolismo , Proteína Wnt1/metabolismo , Angiografia Coronária/métodos , BiomarcadoresRESUMO
Optical coherence tomography of the anterior segment of the eye (AS-OCT) is a non-invasive method based on the principles of optical reflectometry (measurement of the degree of backscattering of light passing through transparent or translucent media). Limitations of the first devices of this type were associated with insufficient image quality of the details of the anterior chamber angle and the posterior parts of the lens, primarily due to the "working" level of the scanning wavelength (within 800 µm). Fundamentally new possibilities in the structural and functional assessment of the anterior segment of the eye are associated with the introduction into clinical practice of swept-source AS-OCT device - the CASIA2 anterior optical coherence tomograph (Tomey Corporation, Japan). Its high scanning speed (50 000 A-scans per second) with a wavelength of 1310 µm allows high-quality visualization by building a scan at a depth of 13 mm. The previous model (CASIA SS-1000, Tomey Corporation, Japan) supported scan depth of only 6 mm. This review summarizes the results of research on the clinical use of CASIA2 tomograph.
Assuntos
Segmento Anterior do Olho , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Humanos , Segmento Anterior do Olho/diagnóstico por imagemRESUMO
Selective keratoplasty involves replacing the affected layers of the cornea with similar donor tissue. In case of pathological changes in the middle and posterior stroma, deep anterior lamellar keratoplasty (DALK) is performed. Chronic corneal edema caused by endothelial dysfunction is an indication for endothelial keratoplasty - Descemet membrane endothelial keratoplasty (DMEK) or Descemet Stripping Endothelial Keratoplasty (DSAEK). Compared to penetrating keratoplasty (PK), these operations are characterized by a low risk of damage to intraocular structures and a relatively short rehabilitation period. Complications of selective keratoplasty include the formation of a false chamber between the lamellar graft and the recipient's cornea, ocular hypertension during anterior chamber air tamponade. Persistent epithelial defect can be a sign of primary graft failure in DALK, DSAEK and DMEK. Selective keratoplasty is characterized by a lower incidence of immune rejection than PK. In some cases, DALK can be complicated by corneal changes related to suture fixation of the graft. Long-term postoperative use of topical glucocorticoids can cause ocular hypertension and cataracts.
Assuntos
Doenças da Córnea , Transplante de Córnea , Humanos , Transplante de Córnea/métodos , Transplante de Córnea/efeitos adversos , Doenças da Córnea/cirurgia , Doenças da Córnea/etiologia , Doenças da Córnea/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Ceratoplastia Penetrante/métodos , Ceratoplastia Penetrante/efeitos adversos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversosRESUMO
The current primary approach to the therapeutic and surgical management of glaucoma is limited to lowering intraocular pressure (IOP). While normalization of IOP stabilizes some functional parameters, there is still potential for further restoration of lost visual function in the post-operative period while maintaining the "therapeutic window". Neuroprotection refers to the modification of retinal ganglion cells and the neuronal microenvironment to promote their survival and function. Numerous studies have identified effective neuroprotective methods for glaucoma; however, their implementation into clinical practice remains a significant challenge. This review presents the most clinically significant treatment strategies, as well as the latest therapeutic advances in physiotherapy.
Assuntos
Glaucoma , Doenças do Nervo Óptico , Modalidades de Fisioterapia , Humanos , Glaucoma/cirurgia , Glaucoma/fisiopatologia , Glaucoma/etiologia , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/terapia , Pressão Intraocular/fisiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapia , Células Ganglionares da Retina/patologiaRESUMO
Effective and atraumatic removal of a soft lens nucleus requires different surgical techniques compared to phacoemulsification of a dense nucleus. PURPOSE: This study was conducted to develop a non-ultrasound technique for emulsification of a soft lens nucleus. MATERIAL AND METHODS: Fifty-seven patients (57 eyes) underwent surgery. In 23 cases, early or immature cataracts were detected, and in 34 cases, lens removal was performed for refractive purposes in high myopia and complex myopic astigmatism. Phacoemulsifier Centurion Vision System (Alcon Laboratories, Inc., USA) was used for the surgery. Aspiration of soft lens nucleus was done using a rotational technique. The following aspects were evaluated in the course of the surgery: the volume of the required irrigation solution, and the frequency needing to involve ultrasound for complete emulsification of the lens nucleus. Intraoperative and postoperative complications were also assessed. RESULTS: The surgery was uneventful in all cases. There were no violations of the integrity of capsulorhexis edge. The need for short pulses of minimal power ultrasound during the removal of the soft lens using this technique arose only in 11 (19.3%) cases. The effective ultrasound time was less than 1 second. The required volume of irrigation solution was 33.0 (24.0; 43.0) ml, which does not differ significantly from that in ultrasonic phacoemulsification. CONCLUSIONS: The use of modern phacoemulsifiers providing a high vacuum level allows successful removal of a soft lens without using ultrasound, which prevents its negative impact on the ocular tissues. The use of adequate surgical techniques, including the optimal direction of rotation of the lens nucleus in the rotational technique, improves the efficiency of soft lens nucleus removal.
Assuntos
Facoemulsificação , Humanos , Masculino , Feminino , Facoemulsificação/métodos , Pessoa de Meia-Idade , Catarata , Resultado do Tratamento , Núcleo do Cristalino/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , IdosoRESUMO
The influence of various patterns of preliminary femtosecond laser-assisted fragmentation of the lens nucleus on the energy and hydrodynamic parameters of phacoemulsification remains insufficiently studied. PURPOSE: This study evaluates the influence of various patterns of preliminary femtosecond laser-assisted fragmentation of the lens nucleus on the energy, hydrodynamic parameters of phacoemulsification, and the degree of corneal endothelial cell loss. MATERIAL AND METHODS: Hybrid phacoemulsification was performed in 336 patients (336 eyes) with grade IV immature cataract according to the Buratto classification in three age-matched groups. Group 1 included 103 patients (103 eyes) who underwent hybrid phacoemulsification with preliminary femtosecond laser-assisted fragmentation of the nucleus with a «pizza¼ pattern (division of the nucleus with 10 radial cuts). Group 2 included 112 patients (112 eyes) who underwent femtosecond laser-assisted fragmentation of the nucleus with a «cylinders¼ pattern (division of the nucleus with 8 radial cuts in combination with 5 circular cuts). Group 3 included 121 patients (121 eyes) who underwent femtosecond laser-assisted fragmentation of the nucleus with a «grid¼ pattern (division of the nucleus with 8 radial cuts in combination with multiple mutually perpendicular cuts in the central zone in the form of a grid with a 0.5 mm cell). Effective ultrasound time and the volume of irrigation solution for emulsification of the lens nucleus fragments were determined during the operation. The loss of corneal endothelial cells was assessed 3 months after surgery. RESULTS: The minimum effective ultrasound time was noted after using the "grid" pattern - 4.05 (2.88; 4.74) s, which was significantly less than with the "cylinders" pattern - 4.97 (3.78; 5.88) s and the "pizza" pattern - 6.15 (4.52; 7.75) s (p<0.05). The effective ultrasound time when using the "cylinders" pattern was significantly less than with the "pizza" pattern (p<0.05). The volume of irrigation solution used for emulsification of the lens nucleus fragments was significantly less in the "grid" pattern - 41.5 (33.5; 49.5) ml compared to the "cylinders" patterns 58.5 (51.0; 66.0), p<0.05 and "pizza" pattern 75.0 (66.0; 83.5), p<0.01. The volume of irrigation solution when using the "cylinders" pattern was significantly less than when using the "pizza" pattern (p<0.05). The loss of corneal endothelial cells after using the "grid" pattern was 8.82 (7.59; 9.87)%, which was significantly less than after the "cylinders" patterns - 9.97 (8.81; 10.83)%, p<0.05 and "pizza" - 11.70 (10.62; 12.97)%, p<0.05. At the same time, the loss of endothelial cells after using the "cylinders" pattern was significantly less than after the "pizza" pattern (p<0.05). CONCLUSIONS: The choice of the optimal pattern of preliminary femtosecond laser-assisted fragmentation of the lens nucleus provides a significant decrease in the energy and hydrodynamic parameters of phacoemulsification and, accordingly, the loss of corneal endothelial cells.