Open Non-randomized Study Research Articles

Predicting Response to Immunotargeted Therapy in Endometrial Cancer via Tumor Immune Microenvironment: A Multicenter, Observational Study.

Only one-third of patients with advanced MSS/pMMR endometrial cancer exhibit a lasting response to the combination treatment of Pembrolizumab and Lenvatinib. The combined administration of these two drugs is based on Lenvatinib's ability to modulate the tumor microenvironment, enabling Pembrolizumab to exert its effect. These findings underscore the importance of exploring tumor microenvironment parameters to identify markers that can accurately select candidates for this type of therapy. An open non-randomized observational association study was conducted at six clinical centers, involving a total of 28 patients with advanced MSS/pMMR endometrial cancer who received Pembrolizumab and Lenvatinib therapy. Using TSA-associated multiplex immunofluorescence, we analyzed the proportion of CD8+ T lymphocytes, CD20+ B lymphocytes, FoxP3+ T regulatory lymphocytes, and CD163+ macrophages in tumor samples prior to immunotargeted therapy. The percentage of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio was significantly higher in patients who responded to treatment compared to non-responders (responders vs. non-responders: 0.24 (0.1-1.24)% vs. 0.08 (0.00-0.15)%, p = 0.0114; 1.44 (0.58-2.70) arb. unit vs. 19.00 (3.80-34.78) arb. unit, p = 0.0031). The sensitivity and specificity of these biomarkers were 85.71% and 70.59%, and 85.71% and 85.71%, respectively. The proportion of CD20+ B lymphocytes and the CD8-to-CD20 lymphocytes ratio in the stroma of endometrial cancer serves as both a prognostic marker of response to immunotargeted therapy and a prognostic factor for progression-free survival in patients.

Evaluation of utero-placental vascularization using contrast-enhanced ultrasound: Early first trimester maternal perfusion of the intervillous space is confirmed

IntroductionThe objective was to confirm and semiquantify the maternal perfusion of the intervillous space between 8 and 13 + 6 gestational weeks (GW). MethodsWe conducted a prospective, multicenter, and nonrandomized open study. Women undergoing voluntary termination of pregnancy at three different gestational ages (Group 8 GW: 8 to 8 + 6 GW, Group 11GW: 11 to 11 + 6 GW and Group 13GW: 13 to 13 + 6 GW) were included, with 14 subjects per group. Women presenting with a personal risk of preeclampsia and/or intrauterine growth restriction were excluded. Contrast-enhanced ultrasound (CEUS) was performed with an intravenous bolus administration of 2.4 mL of microbubbles. The region of interest (ROI) was the entire placenta. The perfusion curves and kinetic parameters, including wash-in perfusion index, peak enhancement and mean transit time, were calculated. ResultsOf the 42 women initially included, interpretable perfusion curves could be obtained for 33. Regardless of the gestational age, contrast was observed in the entire placenta. No significant difference in perfusion parameters was observed between groups. There was an association between signal intensity and both maternal heart frequency and placental location. Signal intensity was decreased when the heart frequency increased (p < 0.05) and when the placenta was in a nonanterior position (p > 0.005). DiscussionWe confirmed the presence of maternal perfusion of the intervillous space as early as 8 GW. No significant increase in perfusion parameters was observed between 8 and 13 + 6 GW. Our observations, in accordance with the previous experiment published by Roberts et al.1, strongly challenge the classic trophoblastic plug theory.

Взаимосвязь факторов риска и показателей индуцированного окисления крови у больных стабильной ишемической болезнью сердца

Exposure on key modified risk factors, mainly hypercholesterolemia, arterial hypertension and diabetes mellitus, is an essential component of successful management of patients with coronary artery disease (CAD). As far as the concept of cardiovascular continuum goes, the predisposing behavioral factors that contribute to the development of these abnormal conditions include smoking, hypodynamia and obesity. Oxidative stress is closely associated with atherogenesis at every stage of progression. An open non-randomized prospective study is conducted. An observational group includes 89 patients with stable CAD. Key risk factors of cardiovascular diseases and their correlation with the values of induced blood oxidation were analyzed. Statistically significant (p &lt; 0.05) positive correlation between hypercholesteremia and coefficient of oxidative activity (r = 0.22), smoking and initial rate of blood oxidation (r = 0.24), maximum rate of blood oxidation (r = 0.25), coefficient of oxidative activity (r = 0.24), diabetes mellitus and time of the initiation period (r = 0.25); negative correlation between smoking and time of the initiation period (r = –0.4) were detected. The results obtained show there is a correlation between a lifestyle and oxidative status of patients with stable CAD. Thus, influence on behavioral risk factors is the most important task of management of patients with cardiovascular pathology.

Correlation between Placido-disc and rotating Scheimpflug keratometric findings before and after corneal crosslinking in children with keratoconus.

To evaluate correlation between Placido-disc and rotating Scheimpflug keratometric findings in children with progressive keratoconus (KC) before and after corneal crosslinking (CXL) and investigate whether these limits of agreement varied according to disease severity. Department of Ophthalmology of São Paulo Hospital, São Paulo, Brazil. Prospective nonrandomized open study. Data obtained using rotating Scheimpflug-based tomography and Placido-disc-based topography devices were collected from preoperative and last follow-up postoperative children with KC operated on using standard CXL protocol. Correlation and agreement analyses were performed between the 2 devices before and after CXL to obtain keratometric (K) findings. 44 eyes from 44 patients aged 8 to 16 years were analyzed at all timepoints. All parameters were found to be strongly correlated before ( r = 0.84 to 0.99, P < .001) and after ( r = 0.93 to 0.99, P < .001) CXL. The mean Scheimpflug measurements of flat K, steep K, Kmax, mean K, and corneal astigmatism were higher than Placido-disc measurements in a preoperative period. This mean difference decreased in postoperative, but, with exception of Kmax and corneal astigmatism, Scheimpflug measurements remained higher. The mean parameter measurements from both devices decreased after CXL; 95% limits of agreement between instruments were wide for all parameters and decreased in postoperative and in mild KC. Keratometry measurements obtained using rotating Scheimpflug and Placido-disc technology were found to be closely correlated but not interchangeable before and after CXL in pediatric patients. Agreement between devices was better after CXL and in mild KC than in advanced KC.

Transepithelial Enhanced Fluence Pulsed Light M Accelerated Crosslinking for Early Progressive Keratoconus with Chemically Enhanced Riboflavin Solutions and Air Room Oxygen.

Purpose: To assess the 3-year clinical results of the 18 mW 7 J/cm2 transepithelial enhanced fluence pulsed light M accelerated crosslinking in the treatment of progressive keratoconus (KC) with chemically enhanced hyper-concentrated riboflavin solutions without iontophoresis and with air-room oxygenation. Setting: Siena Crosslinking Center, Siena, Italy. Methods: Prospective pilot, open non-randomized interventional study including 40 eyes of 30 young adult patients over 21 years old (10 simultaneous bilateral) with early (Stage I and II) progressive KC undergoing TE-EFPL 18 mW/7 J/cm2 ACXL (EFPL M TECXL). The 12 min and 58 s pulsed light (1 s on/1 s off) UV-A exposure treatments were performed with a biphasic corneal soaking using Paracel I 0.25% for 4 min and Paracel II 0.22% for 6 min riboflavin solutions and New KXL I UV-A emitter (Glaukos-Avedro, Waltham, USA) at an air room of 21% oxygenation. All patients completed the 3-year follow-up. Results: CDVA showed a statistically significant improvement in the third postoperative month (Δ + 0.17 d. e.) with a final gain of +0.22 d. eq. AK showed a statistically significant decrease in the sixth postoperative month (Δ − 1.15 diopters). K itmax showed a statistically significant decrease at 1-year follow-up (Δ − 1.3 diopters). The coma value improved significantly by the sixth month (Δ − 0.54 µm). MCT remained stable during the entire follow-up. No adverse events were recorded. Corneal OCT revealed a mean demarcation line depth at 282.6 ± 23.6 μm. Conclusions: Transepithelial enhanced fluence pulsed light M accelerated crosslinking with chemically enhanced riboflavin solution halted KC progression in young adult patients without iontophoresis and no intraoperative oxygen supplementation addressing the importance of increased fluence.

Intralesional Keloid Excision Followed by Single Fraction Electron Beam Radiotherapy and Postoperative Local Steroids: a Non-randomized Open Study on Recurrence Rate

Intralesional Keloid Excision Followed by Single Fraction Electron Beam Radiotherapy and Postoperative Local Steroids: a Non-randomized Open Study on Recurrence Rate

РАННЯЯ ДИАГНОСТИКА ПОСЛЕДСТВИЙ НАРУШЕНИЯ МОЗГОВОГО КРОВООБРАЩЕНИЯ У ДЕТЕЙ С ПЕРИНАТАЛЬНЫМ ГИПОКСИЧЕСКИМ ПОРАЖЕНИЕМ ГОЛОВНОГО МОЗГА

Exposure to hypoxia in the perinatal period leads to significant structural changes in the brain (B), which are reflected in the further neuropsychic development of the child. In this regard, the assessment of the state of brain structures and cerebral circulation in young children using high-tech diagnostic methods is of particular importance. Objective of the study: to analyze the indicators of magnetic resonance imaging (MRI) of B structures for early diagnosis of the consequences of cerebrovascular accident in children who underwent hypoxia in the perinatal period. Materials and methods of research: single-center prospective open non-randomized longitudinal observational uncontrolled study were included in 144 newborns, who were stationed in the intensive care unit and intensive therapy units (ICU) of the Regional Perinatal Center of the Krasnodar Regional Clinical Hospital for severe asphyxia and/or intrauterine hypoxia. Among those included in the study were 76 full-term babies (FTBs) (group 1) and 68 premature newborns (PNs) (group 2). The gestational age (GA) of PNs was 29–37 (32.7±2.6) weeks. The sex composition of the groups (boys/girls) did not differ statistically significantly: n=41/35 – 54%/46% in the 1st group versus n=38/30 – 56%/44% in the 2nd group (p=0.816). All children underwent MRI of the B on 2–10 day of life with the determination of the measurement of diffusion coefficient (DC) in the mode of diffusion-weighted images. Children were observed up to 3 years of age in the follow-up department of the Krasnodar Krai Regional Children's Clinical Hospital. Results: in the PNs group, 35 (51%) GA was 29–32 weeks, in 33 (49%) children – 33–37 weeks. The revealed consequences of hypoxic B damage in children were determined by morphological changes in the nervous tissue and were characterized by objective MRI indicators. Analysis of the data obtained made it possible to identify the ranges of B ADI values, reflecting the subsequent neurological outcome. Further formation of neurological deficits (infantile cerebral palsy, disorders of psychoverbal development, symptomatic epilepsy) was noted in PNs with relatively low DC values 0.69–1.30×10–3mm2/s and 0.64–1.07×10–3mm2/s – for white and gray matter of the large hemispheres of the B, respectively; in PNs with relatively low and relatively high DC values of the white matter of the large hemispheres of the B 1.05–1.24×10–3mm2/s and 1.88–2.00×10–3mm2/s, gray matter of the B cerebral hemispheres 0, 93–1.06×10–3mm2/s and 1.36–1.47×10–3mm2/s. The effect of hypoxia in the intrapartum period was manifested by low DC indices, reflecting manifestations of cerebral ischemia. A significant increase in DC indicators was observed in hypoxic brain damage in the antenatal period and characterized atrophic changes in the nervous tissue. Based on the results of the analysis of B DC indices, reflecting manifestations of cerebral ischemia, statistically significant (p&lt;0.01) direct highly correlated relationships were revealed between the DC indices of the white matter of the cerebral hemispheres and the indices of the DC of the gray matter of the cerebral hemispheres (rxy=0.975), the indices of the DC of the midbrain (rxy=0.714) in FTBs, between the indicators of the DC of the white matter of the cerebral hemispheres and the indicators of the DC of the gray matter (rxy=0.923), the indicators of the DC of the midbrain (rxy=0.787) in the PBs, which indicates the global nature of the hypoxic damage to the B. Conclusions: early diagnosis of cerebrovascular accidents in children using MRI data makes it possible to predict the further neurological outcome of perinatal hypoxic brain injures, contributes to the timely implementation of therapeutic and rehabilitation measures based on an objective assessment of the identified disorders.

МИКРОБИОЛОГИЧЕСКАЯ ХАРАКТЕРИСТИКА ПАТОГЕННОЙ ФЛОРЫ У ДЕТЕЙ С ОСТРЫМ И ХРОНИЧЕСКИМ ПИЕЛОНЕФРИТОМ

The study of dynamically changing antibiotic sensitivity of uropathogenic strains in children with pyelonephritis is of great scientific and practical interest, since the course and outcome of the disease and the success of cure depend on it. Objective of the study: to study the microbial landscape of urine and antimicrobial sensitivity of pathogens in children with acute (AP) and exacerbation of chronic pyelonephritis (CP) for timely correction of empirical antibacterial (AB) therapy. Materials and methods of research: a prospective open non-randomized controlled singlecenter study to study the microbial landscape of urine and antimicrobial sensitivity of pathogens in children with AP and CP was conducted at the Speransky Children's City Clinical Hospital No. 9. Inclusion criteria: compliance with the diagnostic criteria for the onset of AP and CP, age from 1 to 14 years, the possibility of assessing the microbiological spectrum of urine before starting AB therapy, determination in urine cultures of strains producing extended spectrum betalactamases (ESBL) and/or carbapenemases (CP-CRE). Results: 552 results of urine bacteriological tests were analyzed. Bacteriuria was detected in 68,3% (n=376) patients, of which 161 (42,8%) were diagnosed with AP, 215 (57,2%) with CP. The structure of pathogens was dominated by gram-negative flora (53,8–70,8%), among which enterobacteria prevailed (79,5%), the dominant microorganism was E. coli (48%). Gram-positive microflora was represented by Enterococcus faecalis (35%). Among enterobacteriaceae, there was a statistically significant increase (p&lt;0,05) in the number of ESBL and/or CP producers, as well as their associations, from 8,8% in 2016 to 25% in 2019–2020 with a peak increase of up to 31% in 2018. A study of resistograms noted that E. coli retains high levels of sensitivity to amoxicillin/clavulanate, however, since 2019, a high frequency of ceftriaxone-resistant strains has been recorded, and in 2020, the detection rate of resistant strains has increased to cefotaxime of E. coli strains. The highest and most stable activity against E. coli ESBL was shown by meropenem and ertapenem. There is a tendency towards a decrease in the sensitivity of Kl. pneumoniae to amoxicillin/clavuanate, fosfomycin and amikacin. The emergence in 2020 of strains of Enterococcus faecalis resistant to amoxicillin/clavuanate and a tendency to a decrease in sensitivity to gentamicin while maintaining a high sensitivity to amikacin were recorded. Conclusion: the results obtained indicate the importance of monitoring the AB-sensitivity of uropathogenic strains in order to increase the effectiveness of empiric therapy and reduce the prescription of inactive antibacterial drugs in children with AP and CP.

АНАЛИЗ АКТИВНОСТИ СИГНАЛЬНОГО ПУТИ ИНТЕРФЕРОНА-I У ДЕТЕЙ С СИСТЕМНОЙ КРАСНОЙ ВОЛЧАНКОЙ: РЕЗУЛЬТАТЫ ПИЛОТНОГО ПРОСПЕКТИВНОГО ИССЛЕДОВАНИЯ

The interferon system (IFN) is a group of signaling molecules with antiviral, antitumor and antiproliferative effects. The most studied signaling pathway is mediated by IFN type I. Mutations of IFN-I-regulated genes are involved in the pathogenesis of systemic lupus erythematosus (SLE). Interferon index (IFN-I-index) – a quantitative indicator of the level of expression of IFN-Iregulated genes – is used to assess the activity of the interferon system. Objective of the study: to assess the level of the IFN-I index in children with SLE, as well as to compare the clinical and laboratory characteristics of patients with high and normal levels of the IFN-I-index. Materials and methods of research: 40 patients (girls – 83%, boys – 17%) under 18 years of age with SLE diagnosed in accordance to the SLICC 2012 criteria were included in a multicenter prospective open uncontrolled nonrandomized continuous study. The age of the patients was 15,2 (12,5 ; 16,7) years. All of them underwent examination and treatment in the Pediatric department № 3 at the clinic of the St. Petersburg State Pediatric Medical University and in the Pediatric department of the Almazov National Medical Research Center. The IFN-I index was determined by real-time PCR with a quantitative assessment of the expression of 5 genes induced by IFN-α and β. Results: aggravated family history of rheumatic diseases was noted in 8 patients: SLE – in 3 (8%), rheumatoid arthritis – in 3 (8%), cold urticaria – in 2 (5%). The average age of onset of the disease is 12 years. The most common clinical manifestations were lesions of the skin, joints, mucous membranes, central nervous system, kidney and fever. 31 patients (78%) had an increased IFN-I index. All cases of kidney failure were observed only in patients with a high IFN index (36% vs 0%, p=0,036). Patients with increased IFN-I-index had statistically significant increased levels of antinuclear (87% vs 56%, p=0,043) and rheumatoid factors (36% vs 0%, p=0,036), higher ECLAM index values (3,0 vs 1.0, p=0,048), ferritin levels (p=0,0008) and, as a consequence, the need for more intensive immunosuppressive therapy (using rituximab and cyclophosphamide) compared with patients with normal IFN-Iindex. A positive statistically significant correlation of the IFN-I index with male sex (r=0,41, p=0,008), nephritis (r=0,35, p=0,026), livedoid rash (r=0,38, p=0,017 ), Raynaud's phenomenon (r=0,37, p=0,018), high antinuclear factor (r=0,82, p=0,001), rheumatoid factor (r=0,654, p=0,011), antibodies to Sm antigen (r=0,57, p=0,034), as well as a negative relationship with anemia (r=–0,67, p=0,009). Conclusion: IFN-I-index can be considered as a surrogate biomarker of activity and prognosis of SLE. Further research is required to validate its diagnostic role.

НЕИНВАЗИВНЫЕ МАРКЕРЫ ФИБРОГЕНЕЗА У ДЕТЕЙ С ОСТРЫМ И ХРОНИЧЕСКИМ ВТОРИЧНЫМ ПИЕЛОНЕФРИТОМ

Objective of the study: to study the clinical significance of the determination of angiotensin 2 (Ang II) and transforming growth factor β1 (TGF-β1) in urine of children with acute and chronic secondary pyelonephritis (PN) for increasing the efficiency of diagnosis of the disease. Materials and methods of research: a prospective open non-randomized controlled longitudinal single-center study was carried out in the Speransky City Children’s Hospital № 9 from January 10, 2015 to June 2020 to study the sensitivity and specificity of the tests under study. 60 children from 1 to 15 years old with acute and chronic secondary PN were examined. Children were divided into 2 groups: 1st – 30 patients with the onset of acute PN, 2nd – 30 patients with recurrent chronic secondary PN. The control group consisted of 20 apparently healthy children. In the 1st group of patients, girls predominated (24 children, 80%), the median age was 7 [3; 9] years, the median duration of followup is 41 [8; 45] months from the onset of the disease. In the 2nd group girls also predominated – 23 (77%), the median age – 8 [5; 11] years, the median duration of the disease at the time of inclusion in the study was 5 [3; 9] years. Most children were diagnosed with vesicoureteral reflux (VUR): grade I–II – in 18 (60%) and grade II–III – in 7 (23%). Incomplete renal doubling was detected in 4 (14%) patients, complete – in one (3%). The control group mainly consisted of girls – 16 (80%), the median age – 5,5 [3,25; 8,75] years. All patients underwent a study of general clinical and biochemical blood test, general analysis of urine, determination in a single morning portion of urine by enzyme immunoassay method according to ELISA TGF-β1 and Ang II. To standardize the level of TGF-β1 and Ang II in the urine, the level of creatinine in each portion of urine was determined and the results were converted to 1 mg of creatinine. Instrumental examination included ultrasound of the kidneys and bladder before and after micturition. Static nephroscintigraphy was performed 6 months after the onset of the disease or recurrence of chronic secondary PN. Results: it was found that at the onset of acute PN and with relapses of chronic secondary PN, there was an increased urinary excretion of TGF-β1 (p=0,002) and Ang II (p=0,002) when compared with the control group. It was shown that the level of increase in these markers depended on the form of PN. There were statistically significant differences in the urinary excretion of TGF-β1 and Ang II in children with acute PN and exacerbation of chronic secondary PN prior to the initiation of antibiotic therapy (p=0,001 and p=0,001, respectively). Urinary levels of Ang II and TGF-β1 in patients with exacerbation of chronic secondary PN in the first days of the microbial-inflammatory process in the renal parenchyma were by an order of magnitude higher than those in children with the onset of acute PN. A high degree of correlation was revealed between the level of uAng II/Cr and uTGF-β1/Cr (r=0,75, p=0,0001 and r=0,89, p=0,0001, respectively) in the 1st and 2nd groups of children (r=0,86, p=0,0001 and r=0,75, p=0,001, respectively) in the acute phase of the disease before antibiotic therapy with the data obtained during static nephroscintigraphy in the period of remission of the disease. Conclusion: the results indicate the importance of studying the urinary excretion of Ang II/Cr and TGF-β1/Cr as additional diagnostic markers for the identification of patients with a relapse current of PN, as well as to predict the degree of development of sclerotic processes in the renal tissue in children with different forms of PN.

Long term results of accelerated 9\u2009mW corneal crosslinking for early progressive keratoconus: the Siena Eye-Cross Study 2

PurposeTo assess clinical results of the 9 mW/5.4 J/cm2 accelerated crosslinking (ACXL) in the treatment of progressive keratoconus (KC) over a span of 5 years.MethodsThe prospective open non-randomized interventional study (Siena Eye-Cross Study 2) included 156 eyes of 112 patients with early progressive KC undergoing the Epi-Off 9 mW/5.4 J/cm2 ACXL at the Siena Crosslinking Centre, Italy. The mean age was 18.05 ± 5.6 years. The 20-min treatments were performed using the New KXL I (Avedro, Waltham, USA), 10 min of 0.1% HPMC Riboflavin soaking (VibeX Rapid, Avedro, Waltham, USA) and 10 min of continuous-light UV-A irradiation. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), Kmax, coma, minimum corneal thickness (MCT), surface asymmetry index (SAI), endothelial cell count (ECC) were measured, and corneal OCT performed.ResultsUDVA and CDVA improved significantly at the 3rd (P = 0.028), Δ + 0.17 Snellen lines and 6th postoperative month, respectively (P < 0.001), Δ + 0.23 Snellen lines. Kmax improved at the 6th postoperative month (P = 0.03), Δ − 1.49 diopters from the baseline value. Also, coma aberration value improved significantly (P = 0.004). A mild temporary haze was recorded in 14.77% of patients without affecting visual acuity and without persistent complications. Corneal OCT revealed a mean demarcation line depth at 332.6 ± 33.6 μm.ConclusionThe 5-year results of Epi-Off 9 mW/5.4 J/cm2 ACXL demonstrated statistically significant improvements in UCVA and CDVA, corneal curvature and corneal higher-order aberrations which confers a long-term stability for progressive ectasia. Based on the results of the Siena Eye-Cross Study 2, the 9 mW/5.4 J/cm2 ACXL is a candidate to be the natural evolution of Epi-Off CXL treatment for the management of early progressive corneal ectasia, and thus optimize clinic workflow.

МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКАЯ ХАРАКТЕРИСТИКА КОМПОНЕНТОВ СИСТЕМЫ КОМПЛЕМЕНТА ПРИ ТЯЖЕЛОЙ ФОРМЕ АКНЕ

It has been shown that the inflammatory response in acne develops at the early subclinical stages of the disease, sometimes before the formation of comedones. It is known that an important component of the innate immune system is the complement system, which includes more than 60 components, including 9 basic proteins (C1-C9), a variety of activation products (C3a, C3b, iC3b, C3d and C3dg), regulatory and inhibitory molecules [factor H, fH-like protein 1 (FHL1), CR1 (CD35), C4b-binding protein (C4BP), C1inh and vitronectin], proteases and secreted enzymes (factor B, factor D, C3bBb and C4bC2b), as well as receptors for effector molecules [C3aR, C5aR, C5L2 and C1q receptor (C1qR)]. The compliment is the central part of innate immunity, which is the first line of protection against alien and altered host cells. The objectives of this study were to determine and analyze the variants of the nucleotide sequence of the genes of the complement system C1QA, C1S, C2, C3, C5, C6, C7, C8A, C8B, C8G, C9 in patients with severe acne. Materials and methods of research: To achieve the target a prospective open non-randomized one-center study was carried out in 2017–2020. Under our supervision in the clinical setting at the Department of Skin Diseases and Cosmetology of the Pirogov Russian National Research Medical University, there were 50 patients in the main group and 20 participants in the comparison group (70 people in total) (42/60% men and 28/40% women) aged 15 to 46 years (median – 22,1 years). Molecular genetic diagnostics was performed in all 70 patients of the main and control groups by the method of high-throughput DNA sequencing – next-generation sequencing (NGS). Results: when analyzing the nucleotide sequence variants of the complement system genes identified in our study, it is shown that the severe form of acne probably has an association (4 SNPs of the C8A gene, 1 SNPs of the C8B gene, 2 SNPs of the C1S gene, 3 SNPs of the C3 gene, 2 SNPs of the C9 gene, 1 SNPs of the C7 gene, 1 SNPs of the C6 gene, 1 SNPs of the C2 gene, 2 SNPs of the C5 gene, 2 SNPs of the C8G gene), 13 SNPs of the complement system genes in introns (1 SNPs of the C8A gene, 1 SNPs of the C8B gene, 2 SNPs of the C1S gene, 1 SNPs of the C3 gene, 1 SNPs of the C7 gene, 2 SNPs of the C6 gene, 4 SNPs of the C5 gene, 1 SNPs of C8G gene), 6 SNPs of the complement system genes (2 SNPs of the C8B gene: one SNPs each in the 3'UTR and 5'UTR zones; 3 SNPs of the C3 gene in the 5'UTR zone, 1 SNPs of the C7 gene in the 3'UTR zone). Two mutations of the frame shift of the C2 gene (frameshift deletion) and the C9 gene (rs748464075, frameshift insertion) seem to have a protective effect in the development of acne. Conclusion: the obtained variants of the nucleotide sequence of the genes of the complement system C1QA, C1S, C2, C3, C5, C6, C7, C8A, C8B, C8G, C9, apparently, are associated with the formation of severe acne and cause an imbalance of the components of the complement system. It can cause a defect in chemotactic and phagocytic reactions, and as a result a disturbance of the regulation of the inflammatory reaction with chronization of the skin process occures. Thus, results of studies carried out, revealed – for the first time – polymorphic loci of genes of components of the complement system, the imbalance of which is the pathophysiological mechanism of acne.

Bioimpedance method for monitoring venous ulcers: Clinical proof-of-concept study

Evaluation of wound status is typically based on means which require the removal of dressings. These procedures are often also subjective and prone to inter-observer bias. To overcome aforementioned issues a bioimpedance measurement-based method and measurement system has been developed to evaluate the state of wound healing. The measurement system incorporated a purpose-built bioimpedance device, a measurement software and a screen-printed electrode array. The feasibility and the performance of the system and method were assessed in an open non-randomized follow-up study of seven venous ulcers. Healing of ulcers was monitored until the complete re-epithelialization was achieved. The duration of follow-up was from 19 to 106 days (mean 55.8 ± 25.2 days). A variable designated as the Wound Status Index (WSI), derived from the bioimpedance data, was used for describing the state of wound healing. The wound surface area was measured using acetate tracing for the reference. A strong correlation was found between the WSI and the acetate tracing data, r(93) = - 0.84, p < 0.001. The results indicate that the bioimpedance measurement-based method is a promising quantitative tool for the evaluation of the status of venous ulcers.

ELECTRO-PHOTONIC EMISSION ANALYSIS IN FUNCTIONALLY HEALTH RESPONDENTS AND PATIENTS WITH NON-COMMUNICABLE DISEASES

The aim: Of this publication is to evaluate the results of EPEA in functionally healthy respondents and patients with NCDs to deepen fundamental knowledge of Systemic Medicine, increase the effectiveness of measures to prevent and treat NCDs by improving their diagnosis and prevention through the introduction of modern science-intensive technologies. Materials and methods: 114 respondents were included in an open non-randomized controlled study. 66 сcomorbid patients (71% - men; median age - 61(43; 80) years) with verified Ischemic Heart Disease: functional class II-III angina pectoris were included in the Main Group. 78 functionally healthy young people (23% - men; median age - 23(20; 30) years) who did not play sports regularly were a Control Group. EPEA was made on a digital software hardware device Bio-Well 2.0 (Bio-Well 2.0, Russia-USA). Results: Significant differences in AEFE indicators in functionally healthy individuals and patients with NCDs were established. Qualitative indicators of AEFE (indicators of area, intensity, energy of emission) were significantly higher in functionally healthy individuals compared to patients with NCDs. Geometric indicators of AEFE (indicators of length of contours and radii of luminescence) were significantly higher in patients with NCDs than in healthy individuals, which confirmed the visually uneven and more complex contour of luminescence of the fingers in them. Conclusions: AEFE parameters have significant differences in functionally healthy individuals and patients with NCDs. AEFE is a fundamentally new promising approach to assessing the level of activity of metabolic processes at the tissue level in living biological systems, including in the normal human body and in patients with NCDs.

Инфекция, вызванная вирусом гепатита С, с наличием криоглобулинемии: особенности и проявления

Study Objective: To study the incidence of cryoglobulinemia (CGE) in chronic hepatitis C infection (hepatitis C infection) and to analyse the characteristics of chronic hepatitis C infection with CGE in Belarusian patients. Study Design: Open non-randomised observational study. Materials and Methods. The study included 773 patients with chronic hepatitis C infection (in Minsk). The patients had their anti-hepatitis C antibodies, chronic hepatitis C RNA and virus genotype measured; blood cryoglobulins identified; demographic and epidemiological data collected; and complete blood assay and biochemical blood assay performed. Study Results. 282 (36.5%) subjects had positive blood cryoglobulins test, while 491 (63.5%) patients had negative result. CGE and non-CGE groups had comparable sex, BMI and infection duration parameters. CGE patients had statistically more surgeries (р &lt; 0.001), clinical syndromes (including asthenovegetative, arthralgic and dyspeptic syndromes, р &lt; 0.001 in all cases), hepatic fibrosis F3 (р &lt; 0.05), hepatic cirrhosis (р &lt; 0.001), and extrahepatic diseases (EHDs); more often they had genotype 3 of hepatitis C infection (р &lt; 0.05) and low replicative activity of the virus (р &lt; 0.05). Conclusion. The incidence of CGE in the study population made 36.5%. CGE patients had more pronounced hepatic process chronization, frequenter EHDs, more genotype 3 cases, and lower replicative activity of the virus. Keywords: hepatitis С, hepatic cirrhosis, cryoglobulinemia, extrahepatic diseases.

Психотерапия у пациентов пожилого возраста c аффективными расстройствами в исходе патологической реакции горя

The relevance of the work is due to the high prevalence and insufficient degree of study of the outcomes of the pathological reaction of grief (PRG) at a late age. Approaches to the treatment of these disorders, often carried out without taking into account the age factor, are not sufficiently developed. The various psychotherapeutic techniques used in PRG are contradictory and poorly structured. Solving these problems will not only achieve good quality remissions, but also prevent endogenization and chronification of mental disorders. The appearance of a new coronavirus infection, accompanied by high mortality, makes the problem of PRG therapy particularly relevant. Objective: to study the features of psychotherapy of depression in late-aged people with a history of PRG. Design: the work is a fragment of an open non-randomized study of patients with PRG, conducted in the Department of geriatric Psychiatry of the Federal State Budgetary Institution of the National Research Center. Inpatient patients over 60 years of age were studied. The clinical-psychopathological and catamnestic methods were used. Pharmaco-and psychotherapy was used. Results: 60 patients were examined, the majority were women, the average age was 66 years, patients with a first — time depressive episode prevailed-45% and recurrent depressive disorder — 28%. The majority (97.7%) of patients had delayed symptoms of PRG. The features of personality, age factors affecting the course of the disease and the peculiarities of psychotherapy are analyzed. Conclusions: the use of an integrated approach (a combination of psychopharmacotherapy and various types of psychotherapy) to the treatment of depressive disorders in the outcome of PRG is justified.

Optimal Organ Protection and Blood Pressure Control with the Single Pill Combination Lisinopril, Amlodipine and Indapamide in Arterial Hypertension

Aim. To evaluate the single pill combination with lisinopril, amlodipine and indapamide ability in additional angioprotection achievement in patients with arterial hypertension and high pulse wave velocity (PWV) regardless on previous antihypertensive therapy (AHT).Material and methods. To the open non-randomized study duration 12 weeks 40 patients were included taking triple AHT during 6 months. All participants underwent ambulatory 24 hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), pulse wave velocity assessment, laboratory tests (HbA1c, serum uric acid, high sensitive C-reactive protein [hsCRP], serum uric acid).Results. We observed additional systolic BP (SBP) and diastolic BP (DBP) reduction by 16.9% and 22.11% on lisinopril, amlodipine and indapamide single pill combination. Lisinopril, amlodipine and indapamide single pill combination decreased 24 h mean SBP by 16.77%, and 24 h mean DBP -23.5% (ABPM data), PWV by 19.7%, augmentation index by 14.81%, central SBP by 11.9% (p&lt;0,05). There were positive changes in hsCRP level (-13.0%, p&lt;0.05) and serum uric acid (-9.0%, p&lt;0.05).Conclusion. Lisinopril, amlodipine and indapamide single pill combination provided control BP, arterial elastic properties improving (augmentation index, PWV, central BP) and favorable influence on inflammation and serum uric acid level.

Altered vascular stiffness and central pulse wave parameters in climacteric women

Aim: to assess changes in parameters of vascular stiffness, central aortic pressure (CAP) as well as reflected pulse wave in women in different phases of the climacteric period.Materials and Methods. An open non-randomized single-center comparative study was conducted with 384 menopausal women subdivided into: Group 1 – 168 women at menopausal transition, Group 2 – 216 women at early postmenopause. A 24-hour blood pressure (BP) monitoring was performed with assessing daily dynamics of parameters of arterial stiffness, CAP and reflected pulse wave. The aortic pulse wave velocity and local aortic stiffness were estimated.Results. It was found that women in early postmenopausal period vs. menopausal transition showed significantly higher values of daily central BP combined with more prominent changes in vascular stiffness. Menopausal women were characterized by lowered difference between nocturnal central and peripheral BP level (less amplified nocturnal vs. diurnal peripheral BP magnitude), which is associated with a greater augmented CAP at this time point. Such pattern was more pronounced in women at postmenopausal period.Conclusion. Women in climacteric period were found to have increased vascular stiffness combined with elevated CAP, decreased amplification of pulse pressure and increased amplitude of the reflected pulse wave may be associated with increased risk of cardiovascular complications. Much more prominent changes were noted in women in early postmenopausal period.

Automated RBC Exchange has a greater effect on whole blood viscosity than manual whole blood exchange in adult patients with sickle cell disease.

Blood transfusion is the cornerstone treatment to reduce the clinical severity of sickle cell disease (SCD), but we need to maintain the haematocrit (Hct) within an acceptable range to avoid a deleterious increase in blood viscosity. The aim of this study was to compare the effects of manual versus automated red blood cell (RBC) Exchange on haematological parameters and blood viscosity. This prospective, single-centre, open nonrandomized observational study included forty-three sickle cell patients: 12 had automated RBC Exchange and 31 manual RBC Exchange. Samples were collected in EDTA tubes just before and within one hour after the end of the RBC Exchange to measure the haematological parameters and blood viscosity. Both automated and manual RBC Exchange decreased haemoglobin S levels and leucocyte and platelet counts, but the decrease was greater for automated RBC Exchange. Manual RBC Exchange caused a significant rise in haematocrit and haemoglobin levels and did not change blood viscosity. In contrast, automated RBC Exchange decreased blood viscosity without any significant change in haematocrit and only a very slight increase in haemoglobin levels. The change in blood viscosity correlated with the modifications of haematocrit and haemoglobin levels, irrespective of the RBC Exchange procedure. When adjusted for the volume of RBC Exchange, the magnitude of change in each biological parameter was not different between the two procedures. Our study demonstrates that the automated RBC Exchange provided greater haematological and haemorheological benefits than manual RBC Exchange, mainly because of the higher volume exchanged, suggesting that automated RBC Exchange should be favoured over manual RBC Exchange when possible and indicated.

The experience with repetitive peripheral magnetic stimulation in subjects with lumbosacral radiculopathy

Introduction. Lumbosacral radiculopathy is а leading cause of long-term disability. Taking into a consideration the duration of treatment radiculopathy, the risk of developing adverse reactions when taking analgesics, non-steroidal anti-inflammatory drugs, the physiotherapeutic method — repetitive peripheral magnetic stimulation may become a promising method of therapy.Aim of the study. Assessment of the effectiveness of the complex treatment for patients with lumbosacral radiculopathy using the course of the repetitive peripheral magnetic stimulation.Materials and methods. Forty patients with lumbosacral radiculopathy were enrolled in the open non-randomized study, were divided into 2 parallel groups. The patients of the 1st group received a course of traditional treatment and a course of the repetitive peripheral magnetic stimulation. The patients of the 2nd group were treated with the traditional treatment without the course of the stimulation. A magnetic stimulator MagPro (Magventure, Denmark) was used for repetitive peripheral magnetic stimulation.Results. A significant difference (p &lt;0.001) was registered regarding the reduction of pain syndrome and the improvement of the functional status after treatment in both groups. 14 (70 %) patients of the first group achieved a pain visual analogue scale relief by 50 % after 10 repetitive peripheral magnetic stimulation sessions, while 6 (30 %) patients did this after 15 repetitive peripheral magnetic stimulation sessions. We did not observed a statistically significant differences (p &gt;0.05) in pain syndrome, functional status, anxiety level at the end of follow-up between the groups.Conclusion. We did not receive the benefits of the repetitive peripheral magnetic stimulation course in comparison with a traditional treatment of a lumbosacral radiculopathy. Further placebo-controlled studies to study the effect of repetitive peripheral magnetic stimulation on pain and anxiety in patients with back pain and radiculopathy are required.