V. V. Moroz’s research while affiliated with Florida Clinical Research Center and other places

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Publications (219)


Prognostic Markers of Acute Suppurative Lung Disease
  • Article

April 2024

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4 Reads

General Reanimatology

D. L. Fetlam

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A. G. Chumachenko

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M. D. Vyazmina

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[...]

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The mortality rate among patients with acute suppurative lung diseases (ASLD) in the ICU reaches 30%. Early, pathogenetically relevant biomarkers are needed to ensure personification and better efficacy of ASLD treatment. Numeric variations in the counts of immune system cells in patient’s blood can be viewed as such candidate biomarkers. The aim of the study. Identification of potential markers predicting ASLD outcome after community-acquired pneumonia and COVID-19. Materials and methods . The study included 216 in-hospital patients aged 18-87 with ASLD after community-acquired pneumonia with (N=81) and without (N=135) COVID-19 history. Results. Patients survival after COVID-19 was linked to lymphocyte count on Day 1 of hospital stay (hazard ratio, HR=5.9 95%CI 0.9–37.4; P=0.0188, log-rank test). In patients who had not have COVID-19, a difference in survival was associated with lymphocyte (HR=2.9 95%CI 1.0–8.4; P=0.0184, log-rank test; N=135), and monocyte counts (HR=2.7 95% CI 0.8–9.5; P=0.0196, log-rank test) on Day 1 of hospital stay. Patients’ survival after COVID-19 infection depended on SII (systemic immune-inflammation index. HR=9.3 95%CI 1.7–49.8; P=0.0124, log-rank test; N=81, SIRI (systemic inflammatory response index, HR=7.2 95%CI 1.4–36.6; P=0.0339, log-rank test; N=81) and NLR (neutrophil-to-lymphocyte ratio, HR=9.6 95%CI 1.8–52.0; P=0.0108; log-rank test; N=81) values on Day 1 of hospital stay. In patients who did not have COVID-19 SII values had no influence on survival. Conclusion. The lymphocyte count makes it possible to predict outcomes of pleural empyema, regardless of patient’s history of COVID-19, i. e. a decrease in the lymphocyte count below 1.2×10⁹ in 1 L is associated with fatal outcome. Monocyte count carries prognostic information for cases of pleural empyema without previous COVID-19 infection. As for the relative indicators, SIRI, SII and NLR values measured on Day 1 in the hospital were predictors of ASLD outcome only in patients after COVID-19 infection, i. e., higher values were associated with increased risk of death, with NLR index being the most informative. Overall severity of illness above 10 scores by CIRS was associated with an unfavorable ASLD outcome, regardless of patient’s history of COVID-19.


Prognostic significance of predictors of early postoperative cognitive disorders in patients after traumatic surgeries (prospective cohort study)

April 2024

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15 Reads

Messenger of Anesthesiology and Resuscitation

The objective was to determine the prognostic value of predictors of early postoperative cognitive disorders in traumatological patients to assess the development of the main clinical outcomes (postoperative delirium and delayed neurocognitive recovery). Materials and methods . A two-center prospective cohort observational study of patients aged 45–74 years after planned traumatological operations (endoprosthetics of large joints of the lower extremities, spinal fusion surgery, transpedicular fixation of vertebrae) under general anesthesia with tracheal intubation was conducted in the period from March 2021 to June 2022. Before the operation, demographic indicators, concomitant diseases, background therapy, laboratory tests and testing (ASA, MoCA, AUDIT, CFS, HADS-A, RASS). At the end of the operation after extubation and in the postoperative period, patients were analyzed according to the scales RUS, CAM- ICU and CAM-ICU-7, NRS and BPS. Statistical analysis was carried out using the software SPSS Statistics 27.0.1.0. Results . The study included 200 patients. Early postoperative cognitive disorders (ePCD) (agitation and emergence delirium (ED)) 61 (30.5%) patients were diagnosed, 139 (69.5%) patients had adequate awakening in the operating room. Independent predictors of the development of ePCD were the age of patients (≥ 60), glucose level ≥ 5.6 and a high score on the Clinical Frailty Scale (≥ 4). The prevalence of postoperative delirium (POD) was 11% (22 patients). The independent risk factors for POD were the duration of hypotension and the presence of hyperactive ED. Delayed neurocognitive recovery after surgery and anesthesia was observed in 115 patients (57.8%). At the same time, a statistically significant predictor of this condition was the duration of hypotension for more than 15 minutes (sensitivity 59.18%, specificity 65.85%). Conclusion . When comparing the influence of the study group (patients with ePCD) with the control group, it was determined that ePCD is an independent risk factor for the development of POD ( p < 0.001).


Sepsis-Associated Metabolites and Their Biotransformation by Intestinal Microbiota

December 2023

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22 Reads

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5 Citations

General Reanimatology

High concentration of sepsis-associated aromatic microbial metabolites (AMM) stands as a prognostically unfavorable factor, indicating the progression of multiple organ dysfunction and an increased risk of death in patients with sepsis and septic shock. This study is based on a hypothesis that excess of sepsis-associated AMM in patients with sepsis is caused by metabolic alterations (dysfunction) in the intestinal microbiota. The aim of this study was to compare the potential of normobiota and pathobiota to bio-transform sepsis-associated metabolites of aromatic amino acids tyrosine and phenylalanine, such as phenyllactic acid(PhLA) and 4-hydroxyphenyllactic acid (4-HPhLA). Materials and methods. Samples of intestinal contents of patients with septic shock ( N =10, pathobiota) and healthy volunteers ( N =9, normobiota) were placed in test tubes with the omnipurpose thioglycol medium. The clinical model of excessive inflow of sepsis-associated AMM into the intestine (for example, from blood or sites of inflammation) was reproduced in the in vitro experiment by adding PhLA or 4-HPhLA in clinically significant concentrations (25 mkM) into each test tube with pathobiota and normobiota. After incubation in a thermostat (37°, 24 hours), AMМ concentrations were measured in the samples with pathobiota and normobiota using GC-MS analysis. Results. Concentration of AMM decreased within 24 hours in the tubes with normobiota after PhLA or 4-HPhLA were added. In the tubes with pathobiota, no decrease in AMM concentrations was documented after loading with PhLA or 4-HPhLA. Concentrations of PhLA ( P =0.002) and 4-HPhLA ( P 0.001) were statistically significantly higher in pathobiota samples compared to normobiota. Conclusion. The in vitro experiment demonstrates that after excessive load with sepsis-associated metabolites (PhLA, 4-HPhLA), the microbiota of healthy people is capable to bio-transform such metabolites to the end products of microbial metabolism, while pathobiota of septic patients exhibits altered biotransformational potential. This data demonstrate that microbiota dysfunction may contribute to the pathogenesis of sepsis.


The 85th Anniversary of the V.A. Negovsky Research Institute of General Rehabilitology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology (Editorial)
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  • Full-text available

October 2021

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16 Reads

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1 Citation

General Reanimatology

Reanimatology (the science of resuscitation) represents the science of critical illness, terminal and postresuscitation conditions, originated within the walls of the V. A. Negovsky Research Institute of General Rean-imatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, turns 85 years old on October 19, 2021. This editorial briefly describes the history of the development of the Institute, as well as the current scientific achievements of the Institute staff.

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Two-step process of cytoskeletal structural damage during long-term storage of packed red blood cells

December 2020

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35 Reads

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19 Citations

Background: Storage of packed red blood cells (PRBC) for 42 days causes morphological, structural, and functional changes in the red cells. To assess the quality of stored PRBC, it is important to evaluate the main components of the product. The aim of this study was to evaluate the kinetics of the structural transformations in the cytoskeleton of red cells during long-term storage (up to 42 days). Materials and methods: Bags of PRBC were stored with CPD/SAGM solution at +4 °C. Cytoskeletal parameters were measured on days 3, 12, 19, 21, 24, 28, 35, and 42 of storage to determine their changes. Atomic force microscopy was used to obtain images and analyse the parameters of the cytoskeletal network. As the storage time increased, a general PRBC test was performed. Membrane fixatives were not used at any stage of the preparation of the specimens for cytoskeletal imaging. Results: When PRBC were stored for 42 days, the main changes to the cytoskeletal mesh included rupture of filaments, merger of small pores into larger ones, a decrease of the number of pores, thickening of filaments, and an increase of membrane stiffness. A process of irreversible changes to the cytoskeleton started on days 19-21. A kinetic model of changes in the parameters of the cytoskeletal mesh with time of PRBC storage was created. Discussion: Two stages of impairment in cytoskeletal elements were found: rupture of filaments and clustering of protein components. The typical time of development and specifics of these stages are discussed. The consequences of the altered configuration of the cytoskeleton are also discussed. Destruction of the red cell cytoskeleton can have a negative effect on the efficacy of blood transfusion and increase the risk of post-transfusion complications. Our findings can be used in clinical medicine to evaluate the quality of PRBC for blood transfusion as well as for studies of the molecular organisation of red cells undergoing various types of physical and chemical treatment.


The relationship of membrane stiffness, cytoskeleton structure and storage time of pRBCs

October 2020

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35 Reads

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10 Citations

Vox Sanguinis

Background and Objectives In clinical practice, it has been shown that transfusion of packed red blood cells (pRBCs) with late shelf life increases the risk of post‐transfusion complications. Objective: To study relationship of membrane stiffness, cytoskeleton structure and storage time of pRBCs. Materials and methods pRBCs were processed and stored according to blood bank procedure, for 42 days, at +4°C; pRBC samples were taken on days 3, 12, 19, 21, 24, 28, 35 and 42. Cytoskeleton images and membrane stiffness were studied using atomic force microscope. Results In the course of the pRBC storage, the cytoskeleton network configuration underwent structural changes. Simultaneously, pRBC membrane stiffness was increasing, with the correlation coefficient 0·88. Until 19 days, the stiffness grew slowly, in 19–24 days there occurred a transition period, after which its growth rate was three times higher than the initial. A chain of pathological processes developed in pRBC during long storage: pH reduction (linked to increased oxidative stress), then cytoskeletal destruction and an associated increase in pRBC membrane stiffness. Conclusion During prolonged storage of pRBCs and their acidification, there is a progression of pRBC cytoskeletal changes and associated increase of membrane stiffness, observed to increase in rate after days 19–24. Mutual measurements of cytoskeletal integrity and membrane stiffness may be useful quality assessment tool to study the molecular mechanisms of RBC structural degradation during storage.


Coronavirus SARS-CoV-2: Hypotheses of Impact on the Circulatory System, Prospects for the Use of Perfluorocarbon Emulsion, and Feasibility of Biophysical Research Methods

May 2020

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62 Reads

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10 Citations

General Reanimatology

This paper highlights published hypotheses on the possibility of coronavirus SARS-CoV-2 entry into the bloodstream, its interaction with vascular endothelium, red blood cells, hemoglobin and its fragments. As a result of such interaction, iron ions may be released into the bloodstream and, subsequently, a cytokine storm may occur. In this context, it is important to find a cytoprotective agent capable of blocking such processes. The perfluorocarbon emulsion could be a candidate for this role. The aim of the paper is to show the feasibility of biophysical methods to study the molecular mechanisms of action of SARS-CoV-2 on human red blood cells and hemoglobin as well as the restorative and cytoprotective effect of the perfluorocarbon emulsion during Fe ²⁺ oxidation in heme. Materials and methods . High resolution spectroscopy, atomic force microscopy, atomic force spectroscopy, electroporation were used. Blood was exposed to oxidizing agents of different nature. Perfluorocarbon emulsion was added in various concentrations and its effect at various incubation times was studied. Concentration of hemoglobin derivatives was calculated considering multicollinearity, and statistical analysis of the results was performed. Results. The perfluorocarbon emulsion was shown to have an effective restorative and cytoprotective action in iron ion oxidation in the heme: Fe ³⁺ was restored to Fe ²⁺ . The degree of MetHb reduction to HbO 2 and Hb depended on the concentration of the oxidizing agent and incubation time. We observed a change in MetHb content from 80-90% to 5-12%. The perfluorocarbon emulsion in clinical concentrations helped eliminate local membrane defects and restored normal erythrocyte morphology. Conclusion. In the light of the studied hypotheses, the use of perfluorocarbon emulsion can become an effective method for blocking the consequences of coronavirus effect on the blood cells and restoring a normal gas exchange.


Experimental setup for detecting the spectrin matrix: schematic representation and AFM images. (a) RBC prior to treatment, (b) haemolysis and partial removal of lipids, (c) formation of RBC ghosts and lipid removal, and (d) exposure of the spectrin matrix on the ghosts’ surface.
Experimental setup for detecting the spectrin matrix: schematic representation and AFM images. (a) RBC prior to treatment, (b) haemolysis and partial removal of lipids, (c) formation of RBC ghosts and lipid removal, and (d) exposure of the spectrin matrix on the ghosts’ surface.
Experimental setup for detecting the spectrin matrix: schematic representation and AFM images. (a) RBC prior to treatment, (b) haemolysis and partial removal of lipids, (c) formation of RBC ghosts and lipid removal, and (d) exposure of the spectrin matrix on the ghosts’ surface.
Experimental setup for detecting the spectrin matrix: schematic representation and AFM images. (a) RBC prior to treatment, (b) haemolysis and partial removal of lipids, (c) formation of RBC ghosts and lipid removal, and (d) exposure of the spectrin matrix on the ghosts’ surface.
Spectrin matrix. (a) Schematic representation of the extracellular membrane surface (arrow A), a dashed line (ZZ) indicates the centre of the membrane. (b) Schematic representation of the inner membrane surface (arrow B) and shifted layer (arrow D). (c) AFM 2D image of the RBC spectrin matrix, 12×12 μm2, obtained with optimised preparation parameters: 300 μL distilled H2O and centrifugation at 3,000 rpm. (d) AFM 2D image of the RBC spectrin matrix, 8×12 μm2, obtained with 500 μL distilled H2O and centrifugation at 3,000 rpm. (e) AFM 2D image of the RBC spectrin matrix on the cytoplasmic membrane surface, 15×15 μm2, obtained with 300 μL distilled H2O and centrifugation at 12,000 rpm. (f–h) Height profiles of the corresponding sections in (c–e). (i–k) Percentage of spectrin network surfaces containing elements <250 nm and > 250 nm, as well as with an undeveloped spectrin network as determined in (c–e, m). (l–m) Percentage of spectrin network on the extracellular membrane surface and with removed or shifted layer: (l) corresponds to (e), and (m) corresponds to (c, d). The dashed line from (b) to (e) delineates the extracellular and inner membrane surfaces. Experimental data are shown as mean±SD.

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Conformational Distortions of the Red Blood Cell Spectrin Matrix Nanostructure in Response to Temperature Changes In Vitro

May 2019

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174 Reads

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10 Citations

Scanning

The spectrin matrix is a structural element of red blood cells (RBCs). As such, it affects RBC morphology, membrane deformability, nanostructure, stiffness, and, ultimately, the rheological properties of blood. However, little is known about how temperature affects the spectrin matrix. In this study, the nanostructure of the spectrin network was recorded by atomic force microscopy. We describe how the nanostructure of the RBC spectrin matrix changes from a regular network to a chaotic pattern following an increase in temperature from 20 to 50°C. At 20–37°С, the spectrin network formed a regular structure with dimensions of typically 150±60 nm . At 42–43°С, 83% of the spectrin network assumed an irregular structure. Finally, at 49–50°С the chaotic pattern was observed, and no quantitative estimates of the spectrin structure’s parameters could be made. These results can be useful for biophysical studies on the destruction of the spectrin network under pathological conditions, as well as for investigating cell morphology and blood rheology in different diseases.


Nosocomial pneumonia — principles of early diagnosis and prevention

April 2019

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34 Reads

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4 Citations

Annals of critical care

Nosocomial pneumonia and nosocomial tracheobronchitis present an urgent problem of anesthesiology and critical care medicine. This review presents the results of our own research on the informativity of new molecular biomarkers in the early diagnosis of nosocomial pneumonia, as well as modern principles for the prevention of nosocomial pneumonia. A promising direction for the early diagnosis of nosocomial pneumonia and its complications is the study of new molecular biomarkers, in particular, Clara cell protein and surfactant proteins. Effective prevention of nosocomial pneumonia should be based on a complex of modern evidence-based methods.


Nonlinear Biomechanical Characteristics of Deep Deformation of Native RBC Membranes in Normal State and under Modifier Action

November 2018

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290 Reads

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15 Citations

Scanning

The ability of membranes of native human red blood cells (RBCs) to bend into the cell to a depth comparable in size with physiological deformations was evaluated. For this, the methods of atomic force microscopy and atomic force spectroscopy were used. Nonlinear patterns of deep deformation (up to 600 nm) of RBC membranes were studied in normal state and under the action of modifiers: fixator (glutaraldehyde), natural oxidant (hemin), and exogenous intoxicator (zinc ions), in vitro . The experimental dependences of membrane bending for control RBC (normal) were approximated by the Hertz model to a depth up to 600 nm. The glutaraldehyde fixator and modifiers increased the absolute value of Young’s modulus of membranes and changed the experimental dependences of probe indentation into the cells. Up to some depth hHz , the force curves were approximated by the Hertz model, and for deeper indentations h>hHz , the degree of the polynomial function was changed, the membrane stiffness increased, and the pattern of indentation became another and did not obey the Hertz model. Quantitative characteristics of nonlinear experimental dependences were calculated for deep bending of RBC membranes by approximating them by the degree polynomial function.


Citations (52)


... In addition, there are a number of aromatic metabolites that are known to be microbial metabolites of these amino acids [20]. Disruption of the microbiota is an important risk factor, leading to imbalance at the microbiome level and affecting the metabolomic profile [28][29][30]. Previously, it was shown that a change in the serum concentration of some aromatic microbial metabolites (AMMs) makes it possible to judge the violation of microbiota metabolism. For example, in patients diagnosed with pancreatic cancer before surgery, the level of some microbial and mitochondrial metabolites is lower than that in healthy volunteers [31]. ...

Reference:

Features of Metabolites and Biomarkers in Inflammatory and Infectious Complications of Childhood Cancers
Sepsis-Associated Metabolites and Their Biotransformation by Intestinal Microbiota
  • Citing Article
  • December 2023

General Reanimatology

... Consequently, this new environment progressively induces a decrease in intracellular high-energy molecules (ATP and 2,3-diphosphoglycerate) as well as antioxidant compounds (NA(D)PH and glutathione), an extracellular accumulation of lactate and potassium, and an increase in lipid and protein oxidation. These changes can lead to the exposure of 'death' signals such as phosphatidylserine and clusters of Band 3, cytoskeleton reorganization and morphological alterations with a progressive release of extracellular vesicles (EVs), a loss of RBC deformability, and haemolysis (Abonnenc et al., 2018;Dinkla et al., 2014;Freitas Leal et al., 2020;Ghodsi et al., 2023;Koch et al., 2019;Kozlova et al., 2021). Metabolic alterations are generally reversible following transfusion whereas oxidative and membrane impairments are mainly irreversible (Yoshida et al., 2019). ...

Two-step process of cytoskeletal structural damage during long-term storage of packed red blood cells
  • Citing Article
  • December 2020

... The structure and function of erythrocytes largely depend on the stability of the environmental pH. It was found that alterations in pH levels affect the size and volume of erythrocytes [2,3], the cytoskeletal structure, the morphology, and, consequently, their ability to deform and pass through capillaries [4]. Alkalosis and acidosis represent extreme deviations in the body's acid-base balance that can significantly disrupt homeostasis and lead to severe clinical consequences [5]. ...

The relationship of membrane stiffness, cytoskeleton structure and storage time of pRBCs
  • Citing Article
  • October 2020

Vox Sanguinis

... In COVID-19 patients, the most pronounced associations with fatal COVID-19 were found for decreased HGB and MCHC levels, as well as increased RDW levels, which correlate with the literature data [39][40][41][42][43]. In COVID-19, massive exposure to inflammatory mediators results in erythrocyte destruction and decreased erythropoiesis [44,45], which can lead to anemia. Furthermore, due to the role of iron in viral replication, decreased iron bioavailability is another mechanism for the development of anemia in viral infections [46]. ...

Coronavirus SARS-CoV-2: Hypotheses of Impact on the Circulatory System, Prospects for the Use of Perfluorocarbon Emulsion, and Feasibility of Biophysical Research Methods

General Reanimatology

... та S. аureus, відзначається дуже висока резистентність цих патогенів до антибіотиків. Також можливий збудник може оцінюватися за провідною флорою конкретної установи [22,23]. ...

Nosocomial pneumonia — principles of early diagnosis and prevention

Annals of critical care

... Hence, it is plausible that our technique has captured subtle, temperature-dependent changes in the cytoskeletal network not detectable by complementary, low-frequency techniques. The reported disordering effect of the same temperature changes on the nanostructure of the spectrin matrix, a critical component of the RBC cytoskeleton, lends support to this hypothesis (Kozlova et al., 2019). It is also important to note that, in addition to the cytoskeleton, hemoglobin can contribute to the global cellular elastic modulus measured by the QCM-D. ...

Conformational Distortions of the Red Blood Cell Spectrin Matrix Nanostructure in Response to Temperature Changes In Vitro

Scanning

... As a classic high-resolution biological surface morphologic imaging tool, AFM can reveal the surface morphologic changes of RBCs (Figure 4a). [45,46] Upon testing Young's modulus on 25 native RBCs and UCZR, it was found that Young's modulus of the UCZR group was 14.04 ± 2.86 MPa, which was slight higher than native RBCs of 12.66 ± 2.67 MPa (Figure 4b). ...

Nonlinear Biomechanical Characteristics of Deep Deformation of Native RBC Membranes in Normal State and under Modifier Action

Scanning

... AFM allows quantitative measurements of the membrane surface, as well as the study of morphological structural characteristics and mechanical properties under various diseases [1,[29][30][31][32][33][34], and the impact of exposure to physical and chemical factors [35][36][37][38]. ...

Nonlinear Local Deformations of Red Blood Cell Membranes: Effects of Toxins and Pharmaceuticals (Part 2)

General Reanimatology

... The following PhCAs are potentially involved in the pathological processes: phenyllactic acid (PhLA), phenylpropionic acid (PhPA), phenylacetic acid (PhAA), p-hydroxyphenylacetic acid (p-HPhAA) and p-hydroxyphenyllactic (p-HPhLA) acid. These compounds affect the mitochondrial functions and the phagocyte activity of neutrophils [17,18] and reflect the severity of the bacterial inflammatory process [19]. Additionally, their levels are correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential (Sepsis-related) Organ Failure Assessment (SOFA) scales [20]. ...

PARTICIPATION OF AROMATIC MICROBIAL METABOLITES IN THE DEVELOPMENT OF SEVERE INFECTION AND SEPSIS
  • Citing Article
  • September 2017

Anesteziologiya i Reanimatologiya

... Клинические проявления ЛК варьируют от эпизодической примеси крови в мокроте до жизнеугрожающего профузного кровотечения. В то же время ЛК -процесс динамический, что для определения лечебной тактики предполагает констатацию интенсивности кровотечения на момент принятия решения [11]. С этой точки зрения, наиболее информативными считаются эндоскопические критерии ЛК. ...

Modern methods of diagnosis and treatment of pulmonary hemorrhage
  • Citing Article
  • January 2013

PULMONOLOGIYA