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Fundamental and Clinical Medicine

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Vol 5, No 4 (2020)
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ORIGINAL RESEARCH

8-13 3126
Abstract

Aim. To study the efficiency of IL-6 inhibitor olokizumab in suppressing the inflammation and improving treatment outcomes in patients with moderate COVID-19 pneumonia.

Materials and Methods. We enrolled 48 patients with confirmed COVID-19 pneumonia who had indications for the treatment with olokizumab. Treatment group (n = 29) included patients who received a single subcutaneous injection of olokizumab (0.4 mL, 160 mg/mL) while placebo group (n = 19) included those who did not receive the drug because of contraindications. Inflammatory markers (C-reactive protein, white blood cell count, lymphocyte count, ferritin and D-dimer) have been evaluated on the 1st and the 5th day after the administration of olokizumab. Efficiency of olokizumab was assessed by the treatment outcome and suppression of cytokine storm.

Results. At the 5th day, SpO2 was 90% (88; 92-93) in both groups, yet none of the patients in the treatment group required a mechanical ventilation, in contrast to 21.1% patients in the placebo group (p = 0.001). Inflammatory parameters were also reduced in the treatment group according to the measurements of serum C-reactive protein (5.6 (1.8;13.5) and 23 (17;92.5) mg/L in the treatment and placebo group, respectively, p = 0.0002) and white blood cell count (5.9 (4.8;6.2) and 7.6 (6.6;12 )*109 /L in the treatment and placebo group, respectively, p=0.03). No statistically significant differences were registered regarding serum ferritin (325 (200; 700) and 215 (186; 526) ng/mL, p = 0.41), D-dimer (827 (378; 1940) and 1464 (677; 4600) ng FEU/mL, p = 0.16) and lymphocyte count (1.3 (0.8; 2.1) and 1.5 (1; 2.1)*109 /L, p =0.44). Death was registered in 3.5% and 21.1% of patients in the treatment and placebo group, respectively, (p = 0.05).

Conclusion. Olokizumab ameliorated the progression of COVID-19 pneumonia, improved treatment outcomes and reduced systemic inflammation.

14-20 582
Abstract

Aim. To study the epidemiological patterns of Lyme disease in the Kemerovo Region.

Materials and Methods. We performed a descriptive and retrospective epidemiological study of 3,133 cases to investigate the spread of Lyme disease in the Kemerovo Region during the recent 15 years (2005-2019). 1,000 ticks of the Ixodes genus were investigated for the presence of Borrelia burgdorferi senso lato s. l. and Borrelia miyamotoi DNA, while 98 patients with tick-borne fevers of unknown aetiology were examined to identify the DNA of the causative agents of ixodid tick-borne borrelioses and tick-borne recurrent fevers by PCR. Antibodies to Borrelia in the patient serum were detected by enzyme-linked immunosorbent assay.

Results. In the structure of tick-borne infections over the study period, the proportion of ixodid tickborne borrelioses was 29.88% [95% CI = 27,25- 32,61]. The incidence demonstrated a 2,8-fold increase from 3.2200 / 0000 [95% CI = 3,20-4,57] in 2005 up to 9,2000 / 0000 [95% CI = 12,47-15,31] in 2019. Annually, around 30,000 people suffered from the tick attack. Bite rates ranged from 813.510 / 0000 [95% CI = 804,05-825,50] to 1506.100 / 0000 [95% CI = 1491,57-1520,02]. Two-thirds of the victims were attacked by ticks during the unorganized recreation in the forest, gathering wild plants and working in the garden plots. Lyme disease was characterised by a spring-summer seasonality with a maximum incidence in June. Rural population showed a higher level of ixodid tick-borne borrelioses incidence as compared to the urban population. In age groups, the maximum rates were recorded in the individuals over 40 years of age. Northern territories of the region showed the highest prevalence of ixodid tickborne borrelioses. In a study of 1000 ticks, DNA of Burgdorferi s. l. and B. miyamotoi was detected in 32.5% and 5.2%, respectively. In contrast, B. miyamotoi prevailed in patients with tick-borne fevers (13.26% of positive cases in comparison with 4.08% for B. Burgdorferi s. l. Tick-borne aetiology of the diseases was confirmed by the enzyme-linked immunosorbent assay measurements.

Conclusions. Ixodid tick-borne borrelioses is prevalent in Kemerovo Region, demonstrating an upward and seasonal trend. Risk groups include rural population and those > 40 years of age. A high level of Ixodes persulcatus-mediated transmission of B. burgdorferi s. l. and B. miyamotoi infections was revealed; the latter agent often caused tick-borne fevers of unknown etiology

21-29 691
Abstract

Aim. To investigate the aetiology of community-acquired pneumonia in hospitalised children and to evaluate the accuracy of the methods for its laboratory confirmation.

Materials and Methods. We performed descriptive and cross-sectional epidemiological studies. Results of the rapid immunochromatographic assay (ICT) were compared with those obtained by polymerase chain reaction (PCR).

Results. DNA of Streptococcus pneumoniae and Mycoplasma pneumoniae was found in 65.5% and 13.8% of the patients. Microbial associations were observed in 13.7% of patients (Mycoplasma pneumoniae + Streptococcus pneumoniae, 10.3%; Streptococcus pneumoniae + Haemophilus influenzae, 3.4%). Chlamydophila pneumoniae and SARS-CoV-2 were not detected. The cause of community-acquired pneumonia was not identified in 6.9% of the cases. A diagnostic accuracy of ICT was 27.58% and its sensitivity was relatively small (9.09%; 95% CI 1; 29), compared with a relatively high specificity (85.7%; 95% CI 42; 100).

Conclusions. Rapid ICT assay must be accompanied by the PCR or other diagnostic methods for the diagnosis of pneumococcal community-acquired pneumonia in children.

30-37 688
Abstract

Aim. Despite obesity is defined by a number of indices (body mass index (BMI), waist circumference (WT), waist / hip index (W/H)) which are associated with type 2 diabetes mellitus (T2DM), the clinical diagnosis of obesity is often limited to BMI. Here we investigated whether anthropometric measurements are useful in T2DM screening.

Materials and Methods. We collected the data regarding T2DM, BMI, WT, W/H, amount of visceral fat, and visceral obesity index from 1600 residents of Kemerovo Region, having further compared the prevalence of T2DM in obese individuals in relation to the various anthropometric measurements.

Results. The prevalence of T2DM among obese males varied from 17.0% (W/H ratio) to 22.4% (amount of visceral fat). Among women, T2DM frequency varied from 13.1% (visceral obesity index) to 28.9% (amount of visceral fat). Prevalence of T2DM in non-obese subjects ranged from 1.6% (W/H ratio) to 8.8% (visceral obesity index) in men and from 1.9% (WT) to 8.8% (amount of visceral fat). T2DM was better diagnosed in males if visceral obesity index was exclusively applied. In women, the most precise T2DM diagnosis was achieved in the case of using visceral obesity index and BMI.

Conclusions. Identification of risk groups for T2DM requires addition of visceral obesity criteria (visceral obesity index and amount of visceral fat) to BMI.

38-45 508
Abstract

Aim. To obtain a purified IgG preparation from the plasma of multiparous women and to evaluate its functional activity towards HLA-DR and HLA-G molecules.

Materials and Methods. IgG preparation was prepared by means of affinity chromatography using the DEAE Affi-Gel Blue system. The purity of the isolated preparation was assessed by immunoelectrophoresis. Functional activity of the IgG preparation against HLA-DR and HLA-G molecules was assessed in peripheral blood lymphocytes isolated from 14 apparently healthy men of reproductive age by flow cytometry.

Results. A 30 mL IgG fraction was obtained with a protein concentration of 4.3 g/l and a residual albumin less than 0.1 g/l. The protein concentration in the obtained fraction corresponded to the lower limit of IgG concentration in human serum. Immunoelectrophoresis showed that the IgG was the only antibody fraction in the chromatographic washout. Purified IgG fraction suppressed the expression of HLA-DR and HLA-G in donor lymphocytes.

Conclusion. The purified IgG fraction from multiparous women can have a significant preventive and therapeutic effect against immune disorders in the mother-embryo system and therefore might halt the development of congenital heart defects by blocking HLA-DR and HLA-G in the lymphocytes.

46-56 712
Abstract

Aim. To investigate the association between coronary atherosclerosis and sarcopenia in male patients with coronary artery disease (CAD).

Material and Methods. We enrolled 79 male patients with CAD verified by coronary angiography (median age 63 (57; 66) years). Patients were stratified according to the severity of coronary atherosclerosis: 1) 1 or 2 affected coronary arteries; 2) 3 affected coronary arteries; 3) lesions in the left main coronary artery (LMCA), with or without other coronary arteries involved. Sarcopenia was diagnosed according to the recommendations of the European Working Group on Sarcopenia in Older People (EWGSOP) which include examination examining of muscle strength, mass and function. Patients were also divided into those without sarcopenia (n = 31), those with presarcopenia (n = 21), and those with sarcopenia (n = 27).

Results. Severity of coronary atherosclerosis inversely correlated with the musculoskeletal index (r = - 0.227, p = 0.047). A higher prevalence of LMCA lesions was noted in patients with sarcopenia compared with those with presarcopenia or without sarcopenia (29.6% vs. 20.0% vs. 13.3%, respectively). Severe CAD (3 affected coronary arteries or LMCA lesions was associated with a reduction in the musculoskeletal index with sensitivity of 68.1% and specificity of 56.7% (area under the curve = 0.634; 95% CI: 0.515-0.741; p = 0.028; Youden's index 0.248).

Conclusion. Sarcopenia is associated with increased severity of CAD.

57-64 646
Abstract

Aim. To study the association between the number of neutrophil extracellular traps (NETs) formed by circulating neutrophils and echogenicity of carotid atherosclerotic plaques.

Materials and Methods. We enrolled 72 patients (40-64 years of age) without the clinical signs of atherosclerotic vascular disease, who then underwent ultrasound duplex scanning of carotid arteries. Grayscale median analysis of the images was performed using Adobe Photoshop CS6 software. Neutrophils were stained and examined by means of light microscopy to count NETs.

Results. Carotid atherosclerotic plaques were found in 69.4% of asymptomatic patients. Echogenicity of atherosclerotic plaques inversely correlated with the number of NETs (r = - 0.310; p = 0.029). The number of NETs in patients with echolucent plaques (GSM < 60) was significantly higher in comparison with echogenic plaques (GSM ≥ 60, p = 0.042).

65-75 683
Abstract

Aim. To study psychophysiological parameters in the patients undergoing coronary artery bypass grafting (CABG) who optionally underwent a short course of physical prehabilitation (PPR).

Materials and Methods. We carried out a prospective randomised study which included 97 male patients (45 to 70 years) with coronary artery disease who underwent elected CABG; 47 of them additionally underwent a 5-7-day course of aerobic physical training before the surgery. Both patient groups were comparable with respect to the baseline clinicopathological features. Neuropsychological examination and electroencephalography was performed before the surgery and at 7th-10th day after CABG. Development of postoperative cognitive dysfunction (POCD) was considered as the study endpoint.

Results. POCD developed in 58% patients with PPR and in 78.7% patients without PPR (p = 0.037); therefore, the risk of developing POCD in those who underwent PPR was lower (OR=0,39, р=0,045). Further, patients with PPR showed an increase in integral attention value relative to the preoperative state (p = 0.04) while those without PPR demonstrated a decrease in this cognitive parameter (p = 0.03). Integral attention value and general cognitive status remained higher in patients with PPR than in those without (p = 0.048 and p = 0.048, respectively) at 7th-10th day after CABG. The theta1 rhythm power increase was higher in patients without PPR at 7th-10th day after CABG (p = 0.01).

Conclusion. The patients with a short preoperative course of PPR had better indicators of electrical cortical activity and higher integral cognitive value in the early postoperative period after CABG than those without training. Short course of PPR before CABG can increase the resistance of the brain to the intraoperative injury and may reduce the severity of the cognitive impairment after cardiac surgery. Indicators of brain electrical activity can be informative to evaluate the efficiency of cardiac rehabilitation

76-83 645
Abstract

Aim. To compare the foot position in asymptomatic children and those who received conservative or surgical because of flatfoot.

Materials and Methods. We consecutively recruited three patient groups: 112 healthy children, 74 children with a pronation position, and 80 children with an overpronation position of the foot. The Foot Posture Index (FPI – 6) was used for the clinical examination. Visual and manual clinical tests were used to determine the mobility of the foot joints. X-ray was performed in a standard lateral projection with a load; if necessary, multislice computed tomography of the foot was performed.

Results. Healthy children commonly have pronation position of the foot during the first 10 years of life, with the further normalisation of the posture. In patients receiving conservative treatment of foot pronation, normalisation of the foot position was considerably less pronounced than in healthy children. Further, in those with overpronation position, there were no age-dependent changes in the posture and surgery was the only efficient approach to correct the flatfoot.

Conclusion. FPI-6 is a highly sensitive tool for clinical diagnosis of flatfoot. Moderate pronation has a more favorable prognosis than the overpronation position, which is not corrected during the body growth or by the conservative treatment. Yet, surgery is a safe and efficient approach to relieve the pain syndrome and treat the flatfoot deformity.

84-88 919
Abstract

The stem cell mutations and modification of the tumor microenvironment are the main causes of cancer formation. The neutrophiles extracellular traps (NETs) are the components of the tumor microenvironment. NETs are web-like structures composed of nucleic acids, enzymes, cytoplasmic proteins, and bound pathogens. Currently the information on the pathogenetic role of NETs in the development of chronic noncommunicable diseases is contradictory. There is data of their carcinogenic effect.

Aim. To determine the amount of NETs and the composition of the tumor microenvironment in the cervical smears in patients with precancerous diseases and cervical cancer.

Material and Methods. The clinical group 1 - patients with precancer cervical diseases (n=10), the clinical group 2 – patients with cervical cancer III stage (n=14) were studied. The average age of patients was 38±8.26. The control group was formed of volunteers without cervical pathologies (n=10). Cervical smears were used as the material for the research. The study was compliant with the principles of WMA Declaration of Helsinki, 1964, rev. 2013 and was performed with consent of the Local Ethics Committee of Chita State Medical Academy. Cancer or dysplastic cells, normall cells, immune cells, NETs were counted in Feulgen stained cervical smears by the optical microscope.

Results. There are reducing the proportion of healthy epithelial cells, increasing the pool of immune system cells and the appearance of the NETs in the cervical scraping during cervical cancerogenesis. NETs were visualized In 60% of cervical cancer patients. The statistically significant differences in the content of NF in cervical smears among the group of patients with precancerous diseases of the cervix and the control group did not determinated.

Conclusion. Detection of the NETs in the cervical smears may be a new cytological sign of malignancy of the cervical epithelium. Detection of the NETs in the cervical tumor microenvironment smears may indicate their involvement in cervical carcinogenesis.

REVIEW ARTICLES

89-96 803
Abstract
COVID-19 pandemic provoked an increasing interest in recent advances in diagnosis and treatment of critical care patients. Among the main problems are the lack of evidence-based guidelines and a growing number of patients with multiple organ dysfunction syndrome. Therefore, indications for the use of previously uncommon intensive care approaches are expanding. These reasons, along with a large pool of non-systematic literature, dictate the need in the narrative review of top 10 recent publications which provide a snapshot of the most relevant research in critical care. These papers overview evidence-based information on the control of acute kidney injury, ventilator-associated pneumonia and sepsis in critically ill patients including those with COVID-19, principles of proper haemodynamic and ventilatory support, timely cessation of antimicrobial therapy, efficient prevention of gastrointestinal bleeding, and the use of the prone position in patients with acute respiratory distress syndrome.
97-103 75161
Abstract
For decades, there have been a number of controversial issues regarding the airborne transmission of hospital pathogens. Here we decided to perform a critical review on this topic in light of the current COVID-19 pandemic. We summarise the existing knowledge on biological aerosols including techniques of their generation, propagation of bioaerosol particles in a hospital environment, particle size-, shape- and composition-dependent airborne transmission, and microorganisms inhabitating such particles. It is still unclear which of the particles transfer the pathogens, which of the pathogens are capable of adhering to the particulate matter, and whether such adhesion affects pathogen virulence. Intriguingly, viruses, bacteria and fungi seemingly have distinct patterns of interactions with the bioaerosols. Moreover, particle formation and their colonization may be separated in time, further complicating the puzzle. Apparently, pathogen interactions with the particulate matter are of paramount importance to better understand the role of bioaerosol particles as a potential pathogen reservoir in the hospital environment and to properly assess the influence of environmental pollutants, novel biomedical materials and treatment technologies on airborne transmission of hospital pathogens.
104-116 1422
Abstract
Non-thermal plasma (NTP) in the air around the cell layer or biological tissues is considered as a generator of reactive oxygen and nitrogen species, ions, and solvated/aquated electrons. This review covers current understanding on the effects of NTP in living systems, with the focus on the role of free radicals and other NTP-generated particles in the chemical modification of biomacromolecules and regulation of signal transduction. We summarise recent data on the impact of NTP-originated products on intracellular redox balance, mitochondrial biogenesis, cell membranes and organelles. In addition, we discuss the transport of NTP products across the biological membranes. Since the expression of numerous transporter systems differs at various stages of development, distinct cell lines, and in pathological conditions, experiments on NTP effects should be designed in various models for the assessment of cell- and tissue-specific response. Notably, NTP effects are observed throughout the whole tissue even when particles are generated at the surface. Special attention is paid to the NTP-treated solutions (phosphate buffered saline, Ringer’s solution, cell culture medium) as their composition and pH can be significantly altered. However, these data also suggest novel opportunities for the application of NTP and NTP-treated solutions in biomedicine. Studies on the mechanisms of NTP action on biological systems should contain analysis of events coupled to generation and accumulation of reactive oxygen and nitrogen species, neutral compounds, solvated electrons, and detection of new cellular targets of their action. This would allow developing of efficient and safe protocols for NTP applications in biology and medicine.
117-125 672
Abstract
Renal denervation (RDN) is a method of the sympathetic nervous system modulation which has been specifically developed for the treatment of resistant hypertension. Initial reports demonstrating high efficiency of RDN in such patients propelled the development of the technology, yet a specific randomised controlled trial Symplicity HTN-3 did not show its benefits. Data from the subsequent RCTs SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED have shown that RDN reduces both office and daily blood pressure, does not depend on the patient adherence, and is efficient in patients with uncontrolled hypertension even in the absence of drug therapy. This review summarises the data on the efficacy and safety of the technology, its organoprotective effects, and also discusses the benefits of the RDN in different patient groups.
126-132 1419
Abstract
Along with sleep and meal, sexual function is one of the main human motivations and its impairment can drastically reduce the quality of life in women. This condition is often overlooked and untreated. The prevalence of sexual dysfunction in the female population of different countries ranges from 25 to 63%, being particularly high in Siberia (55.9-69.4%) and southern Russia (45.5%). The most significant risk factors of sexual dysfunction in Russian women are age, stress and menopause. Current data on the impact of the COVID-19 on women's sexual function are limited and contradictory. Here we discuss how COVID-19 pandemic, associated with significant changes in the lifestyle, self-isolation and reduction of income, affected reproductive and sexual health of women in various countries. Generally, sexual activity of women reduced by around 40%, and most studies showed a decrease in libido and sexual arousal. COVID-associated sexual dysfunction also had its features across different populations and social groups. However, none investigated the impact of the COVID-19 pandemic on the sexual health of the female population in the Russian Federation.

LECTURES

133-140 10357
Abstract
Molecular genetic techniques represent an essential part of current biomedical research. Among them, polymerase chain reaction (PCR) is the most widespread. This approach reproduces the natural mechanism of nucleic acid replication in vitro, specifically restricted to the region of interest. PCR permits fast and highly specific amplification of the genome fragments belonging to any organism. Therefore, the applications of PCR diagnostics vary from identifying infectious agents to establishing causes of hereditary and multifactorial diseases and to personal identification in forensic medicine. The proposed lecture course discusses the PCR principles and cases of its application in biomedical research. Here we describe theoretical concepts and molecular basis of PCR diagnostics as well as chemical features of the nucleic acids. Particular attention is paid to the technical solutions extending the applicability of PCR and to the manipulations for its successful use. The lecture is primarily aimed at biomedical students and junior researchers.


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ISSN 2500-0764 (Print)
ISSN 2542-0941 (Online)