Gliflozins position update in the treatment algorithms for patients with type 2 diabetes mellitus and chronic kidney disease: new pathogenetic mechanisms and data from subanalyses of the large randomised control trails

The series of the cardiovascular outcome trails have demonstrated the nephroprotective properties of the gliflozins. Canagliflozin in the CREDENCE, which was the first study with a primary focus on the evaluation of the nephroprotective properties of gliflozin, have demonstrated the possibility to slow the progression of the renal disease. The paper summarizes the additional data from the CREDENCE trail: assessment of the efficacy of canagliflozin by initial eGFR; efficacy in individuals with GFR <30 ml/min/1.73 m2 ; long-term effects of canagliflozin on anaemia-related outcomes; effects of canagliflozin on serum potassium; effects on heart failure and cardiovascular mortality. There are discussed the current treatment algorithms for patients with type 2 diabetes and CKD where using of gliflozins is a priority option. Canagliflozin is a drug with a relatively low ratio of SGLT1/SGLT2 selectivity. The effects of the inhibition of SGLT1 transport in the kidney and in the intestine are described and their additional influence on reducing of the postprandial glycemia and additional nephroprotection

Relationship between the degree of myocardial damage according to contrast-enhanced cardiac magnetic resonance imaging and laboratory data in patients with acute myocardial infarction

Aim. To evaluate the information value of a complex of clinical and biochemical parameters of myocardial damage in predicting the development of transmural myocardial damage according to magnetic resonance imaging (MRI) in patients with acute myocardial infarction (AMI).Material and methods. The study included patients admitted to the emergency cardiology department with acute coronary syndrome. All patients underwent invasive coronary angiography, laboratory tests, and dynamic determination of cardiac biomarkers. In the interval of 6,1±4 days from admission to the hospital, patients underwent contrast-enhanced cardiac MRI. According to the pattern of delayed contrast enhancement, patients were divided into two groups: with a transmural and subendocardial pattern.Results. The mean age of patients was 62,5±10,5 years, while 27 (71,1%) had ST-segment elevation AMI. Among the risk factors for coronary artery disease, dyslipidemia (89,5%), hypertension (68,4%), and smoking (57,9%) were the most common. Creatine phosphokinase-MB (CPK-MB), serum high-sensitivity cardiac troponin I (cTnI) and C-reactive protein (CRP) values after 24 h were significantly higher in patients with transmural hyperenhancement. Moderate positive relationship was found between the global size of left ventricular (LV) damage according to MRI data and the levels of CPK-MB after 24 h and 4 days, as well as with CRP after 24 h, 4 and 7 days, and cTnI level after 24 h and 4 days. In the group of patients with transmural pattern, the global size of LV damage was significantly higher. Patients of this group were characterized by higher prevalence of microvascular obstruction. In a univariate regression analysis, there were following significant predictors of transmural myocardial damage: CPK-MB after 4 days (p=0,023) and ST segment elevation (p=0,029). Multivariate regression analysis showed that the only independent predictor of transmural myocardial damage was an increase in CPKMB after 4 days (p=0,023).Conclusion. An independent predictor of LV transmural damage in AMI was an elevated level of CPK-MB after 4 days. However, this laboratory marker had unsatisfactory information completeness and predictive quality. In this regard, cardiac MRI in patients with AMI, compared with the standard clinical assessment, can be considered preferable for assessing the depth of myocardial damage, risk stratification, and prognosis

Effects of аntimicrobials on <i>Pseudomonas aeruginosa</i> biofilm formation

Pseudomonas aeruginosa is one of the most problematic pathogens in medical institutions, which may be due to the ability of this microorganism to exist in a biofilm, which increases its resistance to antimicrobials, as well as its prevalence and survival ability in the external environment. This work aimed to evaluate the antimicrobial susceptibility of P. aeruginosa strains in planktonic and biofilm forms. We studied 20 strains of P. aeruginosa collected during 2018–2021 by specialists from the Laboratory of Microbiome and Microecology of the Scientific Centre for Family Health and Human Reproduction Problems. The identification of strains was carried out using test systems for differentiating gram-negative non-fermenting bacteria (NEFERMtest 24 Erba Lachema s.r.o., Czech Republic), and confirmed by mass spectrometric analysis and 16S rRNA gene sequencing. Antimicrobial activity was assessed by the degree of inhibition of cell growth in planktonic and biofilm forms (on a flat-bottomed 96-well plastic immunological plate). All clinical isolates of P. aeruginosa were biofilm formers, 47.6 % of the isolates were weak biofilm formers, and 52.4 % of the isolates were moderate biofilm formers. Planktonic cells and the forming biofilm of the tested P. aeruginosa strains were carbapenems-resistant. Biofilm formation was suppressed in more than 90 % of cases by the agents of the cephalosporin and aminoglycoside groups. Antimicrobial susceptibility of P. aeruginosa strains in the formed biofilm was significantly lower (p &lt; 0.05). Carbapenems and cephalosporins did not affect the mature biofilms of the tested P. aeruginosa strains in more than 60 % of cases. Only non-beta-lactam antibiotics (ciprofloxacin and amikacin) suppressed the growth of planktonic cells and destroyed the mature biofilm. The revealed differences in the effect of the tested antimicrobials on the P. aeruginosa strains biofilms correlate with resistance to a number of antibiotics. To prevent biofilm formation in the hospital strains of P. aeruginosa, the use of ceftazidime may be recommended, and antimicrobials such as ciprofloxacin and amikacin may be used to affect mature biofilms of P. aeruginosa

Carotid endarterectomy in Russia. What if current guidelines do not answer difficult questions?

This literature review covers the publications of Russian vascular surgeons in recent years and deals with debatable issues of carotid surgery, including: 1. What is the best technique for carotid endarterectomy (CEA)? 2. Why does restenosis of the internal carotid artery (ICA) develop and how to eliminate it? 3. How to operate on bilateral ICA stenosis? 4. Should carotid glomus be preserved? 5. Is CEA safe in the acute phase of cerebrovascular accident (CVA)? 6. Is CEA safe in elderly patients? 7. How to operate on patients with combined internal carotid and coronary artery involvement? The evidence presented in this publication makes it possible to draw the following conclusions: 1. When choosing a CEA technique, the classical technique with patch angioplasty should be avoided due to the high risk of ICA restenosis. 2. To eliminate ICA restenosis, carotid angioplasty with stenting (CAS) should be used. When performing primary CEA with ICA transposition over the hypoglossal nerve, reCEA can be used 3. In the absence of contraindications, bilateral ICA stenosis can be operated at the same time using CEA. 4. CEA with carotid glomus preservation is the operation of choice in the treatment of patients with hemodynamically significant ICA stenosis due to the elimination of the risks of postoperative hypertension and the formation of hemorrhagic transformation. 5. If there are indications for cerebral revascularization in the most acute period of stroke, CEA should be abandoned in favor of CAS. 6. In old age, CAS is the safest treatment strategy. 7. In the presence of a combined ICA and coronary involvement, the choice of treatment tactics should be carried out only by a multidisciplinary commission, taking into account the risk stratification of adverse cardiovascular events

Inhibition of Soluble Tumor Necrosis Factor Ameliorates Synaptic Alterations and Ca2+ Dysregulation in Aged Rats

The role of tumor necrosis factor α (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4–6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits TNFR1 signaling. Aged rats treated with XPro1595 showed improved Morris Water Maze performance, reduced microglial activation, reduced susceptibility to hippocampal long-term depression, increased protein levels for the GluR1 type glutamate receptor, and lower L-type voltage sensitive Ca2+ channel (VSCC) activity in hippocampal CA1 neurons. The results suggest that diverse functional changes associated with brain aging may arise, in part, from selective alterations in TNF signaling

Canagliflozin: from glycemic control to improvement of cardiovascular and renal prognosis in patients with type 2 diabetes mellitus. Resolution of Advisory Board

Inhibitors of the sodium-glucose cotransporter type 2 (SGLT2i) are a modern class of antihyperglycemic drugs with an insulin-independent mechanism of action. Due to its ability to effectively lower blood glucose levels, improve a number of other cardiometabolic parameters (body weight, blood pressure, uric acid), as well as reduce cardiovascular and renal risks, SGLT2i have become drugs of choice for many of patients with type 2 diabetes mellitus (T2DM). Meanwhile, along with the generally recognized classes-effects of this group of drugs, there are intragroup features, including those associated with their different selectivity in sodium-glucose cotransporters of types 1 and 2 (SGLT1 and SGLT 2). For example, one of the most studied SGLT2i, canagliflozin, in addition to its inhibitory activity against SGLT2, can also moderately block SGLT1 in the intestine and kidneys that could give a maximum efficiency in the control glycemia and others cardiometabolic parameters. In addition, canagliflozin improves not only cardiovascular, but also renal prognosis in patients with T2DM, which is reflected in the corresponding indications in the summary of product characteristics of the drug. This document summarize the established and new data regarding the efficacy and safety of canagliflozin, as well as its place in the treatment of T2DM

Возможности фармакологического лечения остеоартрита: фокус на симптоматические медленно действующие препараты (SYSADOA) и индивидуальные особенности пациента. Резолюция международного совещания экспертов

The paper presents the results of the Osteoarthritis (OA) Expert Council held on September 8, 2019, which was attended by Russian and foreign specialists. The experts considered pharmacological treatment options for OA. The expert meeting resolution states that the treatment of patients with OA should be based on an individual assessment of the patient and on a modern evidence base of therapy efficacy.Treatment of patients with OA is based on the principles of evidence-based medicine that requires an integrated approach and the need of SYSADOAs prescription. Combined drugs with therapeutic dosages of chondroitin sulfate and glucosamine in the early stages of the disease are available as basic agents. The place of paracetamol in the anesthetic therapy algorithm in OA needs to be clarified. It is also noted that when choosing nonsteroidal anti-inflammatory drugs for OA treatment, it is important to take into account individual patient characteristics and the presence of comorbidities.Представлены результаты Экспертного совета по остеоартриту (ОА), проходившего 8 сентября 2019 г., в котором приняли участие российские и зарубежные специалисты. Рассматривались возможности фармакологического лечения ОА. В резолюции совещания указано, что лечение больных ОА должно быть основано на индивидуальной оценке состояния пациента и современных доказательствах эффективности терапии. Лечение больных ОА на основании принципов доказательной медицины предполагает комплексный подход и назначение SYSADOA. Комбинированные препараты с терапевтическими дозами хондроитина сульфата и глюкозамина уже на ранних стадиях заболевания рассматриваются в качестве базисных средств. Место парацетамола в алгоритме обезболивающей терапии при ОА требует уточнения. Отмечено также, что при выборе нестероидных противовоспалительных препаратов для лечения ОА важно учитывать индивидуальные особенности пациента и наличие коморбидных состояний