Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Mayanskiy NA, Brzhozovskaya EA, Stoyanova SS, Frolkov AV, Lebedin YuS

Generation and maintenance of immunity to SARS-CoV-2 is essential for overcoming the pandemic of the novel coronavirus infection COVID-19. The study was aimed to assess the dynamic changes in the levels of IgG antibodies against the SARS-CoV-2 receptor-binding domain (RBD) with the use of the enzyme-linked immunosorbent assay (ELISA) kits, calibrated using the International Standard for anti-SARS-CoV-2 immunoglobulin (IS-SARS-CoV-2). The concentrations of anti-RBD-IgG were measured in the cohort of individuals, who had recovered from COVID-19, with an interval of a month for 6 months, and at a time point of 12 months, using the ELISA kits, calibrated with the use of IS-SARS-CoV-2; the results were expressed in binding antibody units (BAU) per 1 mL. A total of 97 blood serum samples, obtained from 20 individuals with SARS-CoV-2 infection, confirmed by PCR, were collected. The geometric mean titer (GMT) of anti-RBD-IgG was 433 BAU/mL (range 36-25,900 BAU/mL) within a month after the infection. The concentration of anti-RBD-IgG gradually decreased with time and reached the GMT value of 68 BAU/mL by the 12th month; anti-RBD-IgG persisted in 13 individuals (93%) out of 14, examined 12 months after the infection. The standardized quantitative serological data play a vital part in monitoring the immune response and make in easier to compare the studies, providing the basis for seeking the common serological correlate of the protective immunity to SARS-CoV-2.

Received: 2022-02-01

Published online: 2022-02-20

DOI: 10.24075/brsmu.2022.007

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VIEWS 2191

Gumenyuk LN, Golod MV, Silaeva NV, Sorokina LE, Ilyasov SS, Androschyuk NA, Krivoshapko OR, Velilyaev AM, Asanova LN

Gut microbiota is an essential element of maintaining the immune homeostasis, including in individuals with COVID-19. The study was aimed to assess taxonomic changes in the gut microbiota and their relationship with the disease severity and the levels of IL6, IL10, IL17, and TNFα in patients with COVID-19. A total of 110 patients with COVID-19 (index group) and 98 individuals with no COVID-19 (control group) were enrolled to the comparative cross-sectional study. The gut micribiota composition was determined by shotgun sequencing. Blood serum levels of IL6, IL10, IL17, and TNFα were assessed by enzyme-linked immunosorbent assay. The following significant changes in the gut microbiota composition were observed in patients with COVID-19 in contrast to controls: decreased abundance of B. adolescentis (p = 0.048), E. rectale (p = 0.036), F. prausnitzi (p = 0.0002), B. dorei (p < 0.001), and increased abundance of R. gnavus (p = 0.012), Сl. hathewayi (p = 0.003), E. faecium (p = 0.0003). Correlations were established between the abundance of B. dorei and the IL6 levels (r = 0.49; p = 0.034), the abundance of F. prausnitzii and the levels of IL10, IL17 (r = 0.44; p = 0.001 and r = –0.52; p < 0.001, respectively). The abundance of R. gnavus correlated with the TNFα levels, and the abundance of E. faecium was related to the levels of IL6 (r = 0.47; p = 0.002) and TNFα (r = 0.56; p = 0.001). The relationship between the abundance of B. dorei, F. prausnitzii, E. faecium and the higher SHOKS-COVID clinical assessment scale scores was also revealed (r = –0.54; p = 0.001, r = –0.60; p < 0.001 and r = 0.67; p = 0.005, respectively). Targeted correction of gut microbiota may improve the COVID-19 treatment efficacy.

Received: 2022-01-18

Published online: 2022-02-19

DOI: 10.24075/brsmu.2022.006

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VIEWS 2182

Generalova LV, Grigoriev IV, Vasina DV, Tkachuk AP, Kruzhkova IS, Kolobukhina LV, Burgasova OA, Gushchin VA

SARS-CoV-2 specific antibody response is a generally accepted measure of postinfection and vaccination-induced immunity assessment. The dynamics of avidity maturation and neutralizing activity of virus-specific immunoglobulins G during the SARS-CoV-2–associated coronavirus infection was studied in cohorts of vaccinated volunteers and COVID-19 patients. 4–6 months after vaccination, neutralization activity was low compared to hospitalized patients (medians 57.4% vs 86.4%). On the opposite, the avidity indices in vaccinated volunteers were significantly higher (median 76.7%) than among hospitalized patients (median 61.4%). During the acute phase of the disease (14–16 days PI), post-vaccination patients have also higher avidity indices than primary patients (medians 43.5% vs 20.4%). Our results suggest that in long-term perspective antibody affinity maturation rate is higher after vaccination than after a natural infection. We demonstrated that Sputnik V vaccination leads to formation of high-avidity IgG, which persists for at least 6 months of observation. These results also indicate the presence of protective efficacy markers for at least 4–6 months after the vaccination or a previous illness and gives grounds for the half-year time period chosen for booster immunization with Sputnik V in Russia.

Received: 2022-01-23

Published online: 2022-02-16

DOI: 10.24075/brsmu.2022.005

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VIEWS 2413

Meshcheryakova MYu, Kolesnikov EN, Trifanov VS, Timoshkina NN, Snezhko AV, Gvaldin DYu

Microsatellite instability (MSI) characterizes a special molecular genetic subtype of malignancies and is associated with the deficiency of mismatched DNA repair. There are no reliable data on the frequency of MSI in colorectal neuroendocrine neoplasms due to the relative rarity of this cancer type. The prognostic significance of MSI is debatable. The aim of this study was to investigate the frequency of the MSI phenotype among colorectal neuroendocrine neoplasms (NENs) with different primary location, grade and stage. Twenty-nine patients (15 men and 14 women, mean age: 62.5 years) included in the study underwent surgery for colorectal neuroendocrine tumors between 2015 and 2018. The mean follow-up period was 3.8 years. Colorectal NENs were grouped by primary location and stage. The majority of the patients (52%) had stage III cancer at diagnosis. The microsatellite stability (MSS) phenotype was confirmed in 24 patients (83%), whereas the MSI phenotype was observed in 5 patients (17%). All MSI-positive tumors were stage I well-differentiated grade G1 or G2 neuroendocrine tumors (NETs) of the rectum. Overall survival was 50% for patients with stage II MSS-positive NENs of the colon and rectum, 33% for stage III and 0% for stage IV. For patients with stage I MSI-positive NENs of the rectum, overall survival was 100%. Thus, the frequency of MSI-positive colorectal NENs was estimated.

Received: 2022-01-12

Published online: 2022-02-14

DOI: 10.24075/brsmu.2022.004

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VIEWS 2044

Egiazaryan KA, Grigoriev AV, Ratjev AP, But-Gusaim AB, Sirotin IV

Despite the diversity of surgical options for slipped capital femoral epiphysis (SCFE), there is an ongoing search for the technique that would ensure a satisfactory outcome, stable fixation of bone fragments and a low rate of complications. The aim of this study was to improve the surgical technique for SCFE in patients with moderate and severe SCFE. The study included 52 children (16 girls and 36 boys) aged 10-15 years (the mean age was 13.2 years) with chronic severe (Krechmar’s stage III) stable (according to Loder’s classification) SCFE. The control group (n = 16) underwent a classic Imhauser procedure; the main group (n = 36) underwent a triplane osteotomy proposed by the authors of the study. The patients were examined prior to surgery and in the late follow-up period (the mean follow-up time was 4.7 years, ranging from 1 to 10 years). The procedure included a clinical examination, history taking, radiography to measure the slip angle and the severity of the slip, and the Harris hip score to assess hip function. After 4.7 years, both groups demonstrated an increase in the range of motion, in comparison with their preoperative results (p ≤ 0.05), good Harris hip scores (94 points in the main group and 81 points in the control group. Postoperative radiographs showed consolidation of the bone, recovery of the proximal femur anatomy. Leg length discrepancy improved significantly in both groups. The proposed technique for extraarticular osteotomy allows recovering the length of the affected leg, the anatomy and physiology of the hip joint, is simple and less traumatic.

Received: 2022-01-10

Published online: 2022-01-31

DOI: 10.24075/brsmu.2022.003

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VIEWS 2143

Moskalenko AN, Filatov AS, Fedotova EYu, Konovalov RN, Illarioshkin SN

Differentiation between Parkinson’s disease, especially in its early stages, and essential tremor, which is a phenotypically similar movement disorder, still remains an unsolved challenge for neurology. The aim of this study was to assess the diagnostic significance of nigrosome imaging (nigrosomes are dopaminergic neuron clusters in the substantia nigra of the midbrain) using 3T high-resolution SW-MRI. The study was conducted in 20 patients with Parkinson’s disease and 10 patients with essential tremor. Visual analysis of the acquired nigrosome-1 images was performed using a 4-point ordinal rating scale. Differences in sex, age and duration of the disease were calculated using the Fisher exact test and the Mann–Whitney U test. The diagnostic value of the method was assessed using Pearson’s chisquared test. Nigrosome-1 was bilaterally or unilaterally absent in 70% of parkinsonian patients. Less specific changes to the substantia nigra (SN) were observed in two more parkinsonian patients (10%), whose nigrosome-1 appeared reduced in size. By contrast, nigrosome-1 was bilaterally intact in all patients (100%) with essential tremor (p < 0.001). Our preliminary findings demonstrate the high potential of noninvasive nigrosome-1 imaging in the differential diagnosis of Parkinson’s disease and essential tremor.

Received: 2021-12-22

Published online: 2022-01-31

DOI: 10.24075/brsmu.2022.002

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VIEWS 2262

Savinova TA, Bocharova YuA, Chaplin AV, Korostin DO, Shamina OV, Mayanskiy NA, Chebotar IV

Antibiotic-resistant strains of Pseudomonas aeruginosa are a global threat to public health. The knowledge of mechanisms underlying antibiotic resistance is essential to counter P. aeruginosa infections. This study describes the phenomenon of meropenem-induced cross-resistance to colistin in the ATCC 27853 strain of P. aeruginosa. The study was conducted in the specimens of P. aeruginosa grown from the reference ATCC 27853 strain in the medium containing meropenem gradients. Susceptibility of the isolates to carbapenems and colistin was assessed using the agar dilution method; susceptibly to colistin was assessed using the broth microdilution method. A total of 93 P. Aeruginosa isolates were analyzed; of them two demonstrated reduced susceptibility to carbapenems (meropenem, imipenem) and colistin. Whole-genome sequencing of the isolates was performed on a MGISEQ-2000 platform. Missense mutations in the oprD and mexD genes and a nonsense mutation in the phoQ gene were detected. We conclude that exposure of P. aeruginosa to meropenem can lead to cross-resistance to colistin, a last resort drug for P. aeruginosa infections.

Received: 2021-12-27

Published online: 2022-01-19

DOI: 10.24075/brsmu.2022.001

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VIEWS 2438

Nikishina VB, Petrash EA, Kuznetsova AA, Shuteeva TV, Zakharova IA

Cognitive and mnestic impairments have a significant negative impact on the quality of parkinsonian patients’ life. Memory impairment causes changes in the mechanisms of information processing. The aim of this study was to investigate the characteristics of transformations undergone by memorized visual and semantic content during memory consolidation and reconsolidation in patients with Parkinson’s disease. The study was conducted on 32 male patients with PD (ICD code: G20). Among the patients, 9 had rigidity/bradykinesia-d ominant PD, 11 had tremor-dominant PD, and 12 suffered from a mixed type of PD. Short-term memory span was assessed using the 10 words and the visual memory tests proposed by Luria. As stimulus materials we used a symbolic representation of the old Greek letter resembling an owl and a translated excerpt from a Canadian aboriginal epic. Regardless of the PD form, the quality of the memorized information was either altered or completely lost. The mechanisms underlying such transformations differed quantitively depending on the PD form. Transformation of the memorized information occurred in the conditions of both incidental and deliberate memorization and was represented by distortions (substitution of the original content with confabulations) and simplifications of the structural and semantic organization. We consolidated significantly lesser amount of auditory verbal (р = 0.018) and visual (p = 0.029) information. This trend was consistent with the pronounced distortion of content during its retrieval.

Received: 2021-12-02

Published online: 2021-12-31

DOI: 10.24075/brsmu.2021.069

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VIEWS 2124