Reconstruction of bone segment of the glenoid at chronic recurrent anterior shoulder instability using porous titanium nickelide

A method of the surgical treatment of posttraumatic recurrent shoulder instability with bony defects using porous NiTiis presented. We operated 5 patients using this method. Recurrences of dislocation after surgical treatment have not been recorded. The method is an alternative to Latarjet procedure and iliac crest bone grafting. We use computerized tomography data in the preoperative making of NiTi graft. The graft is sawed from billet having a cylindrical shape about 1 cm thick. Than by using the drill we form two screw holes. A prepared graft is subsequently installed in the area of the glenoid bone defect. The advantages of this method are accurate reconstruction of the bony defect, minimal risk of recurrences, absence of resorption, reduction of procedure time

Association of Single Nucleotide Polymorphisms in the IL-18 Gene with Production of IL-18 Protein by Mononuclear Cells from Healthy Donors

IL-18 has proinflammatory effects and participates in both innate and adaptive cellular and humoral immunity. A number of SNPs that influence IL-18 production are found in the gene promoter region. We investigated the association of SNPs in the IL-18 promoter at −607 and −137 with the level of IL-18 protein production by PBMC from healthy donors from Southwestern Siberia. The genetic distribution of these SNPs in the promoter site was established by PCR. IL-18 protein production was determined by ELISA. Our results showed that PBMC from donors carrying allele 137C have lower levels of both spontaneous and LPS-stimulated IL-18 production. In contrast, PBMC from donors carrying allele 607A showed significant increases in spontaneous and stimulated IL-18 production compared to wild type. Our study suggests that the SNPs −607 and −137 in the promoter region of the IL-18 gene influence the level of IL-18 protein production by PBMC from healthy donors in Southwestern Siberia

TCF7L2 gene polymorphism in populations of f ive Siberian ethnic groups

Investigation of the frequencies of functionally signif icant gene variants in the context of medical biology and gene geography is a relevant issue for studying the genetic structure of human populations. The transition from a traditional to an urbanized lifestyle leads to a higher incidence of civilizational diseases associated with metabolic disorders, including type 2 diabetes mellitus. The goal of the present paper is to analyze the frequencies of functionally signif icant gene alleles in the metabolic prof iles of indigenous Siberian peoples to identify the gene pool resilience, evaluate the susceptibility of various ethnic groups to metabolic disorders under changing environmental conditions, and predict the epidemiological situation that may occur in the near future. The study was performed in the monoethnic samples of eastern and western Buryats, Teleuts, Dolgans, and two territorial groups of Yakuts. A real-time PCR was used to determine the frequencies of single nucleotide polymorphisms (SNPs) G103894T, rs12255372, and C53341T, rs7903146 in the TCF7L2 gene. The results obtained were compared to the frequencies identif ied for Russians from Eastern Siberia and the values available in the literature. The frequencies of the polymorphic variants studied in the samples from the indigenous Siberian peoples place them in between Caucasian and East Asian populations, following the geographic gradient of polymorphism distribution. A signif icantly lower occurrence of type 2 diabetes risk alleles TCF7L2 (103894T) and TCF7L2 (53341T) in the samples of indigenous Siberian peoples compared to Russians was observed, which agrees with their lower susceptibility to metabolic disorders compared to the newcomer Caucasian population. Taking into account urbanization, a reduced growth in type 2 diabetes incidence may be predicted in indigenous Siberian peoples, i. e. Buryats, Yakuts, Dolgans, and Teleuts, compared to the newcomer Caucasian population. A further study of population structure with respect to different metabolic prof ile genes is required to better understand the molecular genetic foundations of the adaptive potential of indigenous Siberian peoples

Genetic polymorphism of CYP1A1 and CYP2D6 in populations of Buryats, Teleuts and Russians of Eastern Siberia

The study of the gene polymorphism of the system of biotransformation of xenobiotics is an important area of modern medical and genetic research. The aim of this work is to study the frequency of the alleles of the CYP1A1 (A2455G (*2C), rs1048943), CYP2D6 (A2549del (*3), rs35742686); G1846A (*4), rs3892097) genes of Teleuts (n = 115), Eastern Buryats (n = 132), Western Buryats (n = 280), their Métis (n = 56), and Russians of East Siberia (n = 122). Genotyping was performed using real-time PCR with competitive TaqMan allele-specific probes. The frequency of the CYP1A1*2C (2455G) allele was 28.8 % in the Eastern Buryat, 34.6 % in the Western Buryat, 16.7 % in the Teleut, and 31.3 % in the Métis cohort. The frequency of CYP1A1*2C (2455G) in the Russians of Eastern Siberia (4.1 %) corresponds to the frequency range found in European populations. A high-frequency occurrence of CYP1A1*2C (2455G) among Buryats and Teleuts may be indicative of a higher population-wide risk of diseases influenced by technogenic pollutants – substrates of CYP1A1. The CYP2D6*3 (2549del) allele was not detected in cohorts of indigenous populations, among Russians it was 0.4 %, and it was 2.7 % among Métis. The frequency of CYP2D6*4 (1846A) in Eastern and Western Buryats was 5.3 % and 4.3 %, respectively, for Teleuts it was 7.4 %. It was significantly higher in the Russian population (12 %), and among Métis (9.8 %). The obtained data makes it possible to predict a reduced risk of side effects of drugs and cancer associated with CYP2D6*3 (2549del) and CYP2D6*4 (1846A) in the Buryat and Teleut populations. However, metisation introduces new polymorphic variants into indigenous populations, shifts gene frequencies and changes the degree of risks

The ILE462VAL polymorphism of the cytochrome P450 CYP1A1 gene among Tundra Nenets in Yamalo-Nenets Autonomous Okrug, Nganasans in the Taimyr Peninsula and Russians in Siberia

The work concerns a polymorphism of the cytochrome Р450 CYP1A1 gene, the CYP1A1*2C variant (Ile462Val, rs1048943). This substitution results in a two- fold increase in enzyme activity, which leads to accumulation of active intermediates and increases the risk of DNA mutations and chemically induced carcinogenesis. It has been demonstrated that the 462Val allele may be a risk factor in some oncological and other multifactorial diseases. This study was performed on Tundra Nenets in Yamalo-Nenets Autonomous Okrug (N = 271), Nganasans in the Taimyr Peninsula (N = 186) and Russians in North Siberia (N = 267). The cohorts did not include descendants of mixed marriages. Genotyping was performed using Real-Time PCR with competitive TaqMan allele-specific probes. The frequency of the 462Val allele in the Tundra Nenets cohort was 23.8 % (95 % CI 20.4–27.6 %), which corresponds to the frequency range found in East Asian populations and is higher than the values typical of European populations. The 462Val allele frequency in the Russian cohort was 5.8 % (95 % CI 4.1–8.1 %), which corresponds to the frequency range of European populations. The 462Val allele frequency in the Nganasans cohort was 39.0 % (95 % CI 34.2–44.0 %), which is higher than the frequencies found in European, Asian and African populations. Frequencies of the  462Val variant close to that in Nganasans have been observed in Greenland Inuits, native Americans as a whole and the Southern Chinese. A high-frequency occurrence of the 462Val allele among Tundra Nenets and Nganasans may be indicative of a populationwide risk of diseases influenced by this genetic polymorphism, especially when traditional mainstays are gone or previously unknown ecotoxicants appear in the areas

DETERMINING REFERENCE RANGES FOR TREC AND KREC ASSAYS IN IMMUNE DEFICIENCY SCREENING OF NEWBORNS IN RUSSIAN FEDERATION

In this work, we used a reference population of newborns and sampled dried blood spots on Guthrie cards of 2,739 individual samples to determine the reference intervals for TRECs and KRECs values, in order to diagnose primary immunodeficiency by means of neonatal screening. The median absolute values for TRECs and KRECs were 195 (CI95%: 185-206) and 185 (CI95%: 176-197) copies per μl, respectively; the normalized value for TRECs was 2780 (CI95%: 2690-2840), and for KRECs, 2790 (CI95%: 2700-2900) copies per 2 × 105 copies of the albumin gene or 105 cells. The reference interval was calculated for 99 and 99.9 percentiles of total TRECs and KRECs individual values. Due to asymmetric distribution of data, the outliers were filtered off, using the Tukey’s criterion applied after logarithmic transformation of the data. When analyzing absolute values for TREC/KREC (per μL of blood), no “drop-down” TRECs values were identified; for KRECs, 18 experimental values were excluded from further analysis (from 9.8 to 13.5). The outlying values were not identified among the normalized values of TRECs/KRECs. The obtained reference values for TRECs and KRECs (at the 0.1 percentile level) were, respectively, 458 and 32 per 105 cells, or 23 and 17 per μl of blood samples from neonates

Resolution on the results of Advisory Board “Searching the effective methods of testing and treating patients with NSCLC caused by <i>NTRK</i> gene fusions“

The Advisory Board was held on December 24, 2021. The molecular genetic research lead specialists and national lead oncologists discussed issues of diagnosis of NTRK gene translocations in patients with non-small cell lung cancer (NSCLC), as well as current opportunities for the treatment of patients with NSCLC caused by NTRK gene fusions. The experts reaffirmed the necessity to identify timely patients with NSCLC caused by NTRK gene fusions, as the correct diagnosis of the disease, including the use of modern diagnostic methods of NTRK gene fusion (NGS is the most sensitive and specific method) determines the success of patient treatment. In this regard, it is critical that physicians know the advantages and disadvantages of each molecular diagnostic method used to have the opportunity to choose the best approach in each clinical case. In order to have a clear, well-functioning strategy for managing patients with suspected NSCLC caused by NTRK gene fusion, it is necessary to use molecular genetic tests, as well as include TRK inhibitors (in particular, the drug larotrectinib; at the time publication of the Resolution, the drug larotrectinib is not registered in the territory of the Russian Federation) in the clinical guidelines for the treatment of lung cancer. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor. The clinical studies on larotrectinib have demonstrated high response rates and durable responses in adults and children with tumours associated with NTRK gene fusions, including primary CNS tumours and brain metastases. The objective response rate observed with larotrectinib was 79%, with 16% achieving a complete response and 64% achieving a partial response. At the same time, the median progression-free survival on larotrectinib was 28.3 months, and the median overall survival was 44.4 months

Прогностическое значение наличия в крови циркулирующей опухолевой ДНК как маркера минимального резидуального заболевания при колоректальном раке I–III стадии

Introduction. Studies on non-metastatic colorectal cancer have demonstrated the prognostic role of circulating tumor (ctDNA) after surgery, and the ability to identify patients with the greatest risk of progression. This makes it possible in the future to personalize neoadjuvant and adjuvant treatment.The study objective – to evaluate the correlation of the ctDNA status before and after surgery with a clinical outcome in patients with stage I–III colorectal cancer.Materials and methods. The study included data from patients with morphologically verified colorectal cancer with stage I–III who were treated at the N. N. Blokhin National Oncology Research Center in the period from 2016 to 2021. Blood samples were collected before and after surgical treatment (on the 7–10th day after surgery). The minimum permissible concentration at which ctDNA in a plasma sample was considered positive was 0.4 copies of mutant DNA in 1 mcL of plasma. The main criterion of effectiveness was disease-free survival (DFS). The presence of cDNA before and after surgery was a negative prognostic factor for progression in stage I–III of CRC. Patients with positive cDNA after surgery had worse DFS results despite adjuvant chemotherapy. Patients with stage II CRC with negative ctDNA, regardless of adjuvant CT after surgery, did not have disease progression in 100 % of cases.Results. The study included 146 patients with stage I–III colorectal cancer. Progression was detected in 34 patients. The median follow-up time was 22 months (0–66 months). Data on progression were known in 119 patients. Positive cDNA data were detected before surgery in 55 of 120 patients (45 %), after surgery in 46 of 119 (38.6 %). In the group with positive cDNA before surgery, the median DFS was 35 months (95 % confidence interval (CI) 24,0–45.9), in the group with negative cDNA before surgery, the median DFS was not achieved (hazard ratio (HR) 4.6; 95 % CI 2.0–10.4), 1‑year DFS in the cDNA positive group was 62 % versus 100 % in the cDNA negative group (p &lt;0.001). In the group with positive cDNA after surgery, the median DFS was 20 months (95 % CI 8,1–31,9), in the group with negative cDNA was not achieved (HR 27,7; 95 % CI 6,6–116,6; p &lt;0,001). Patients with positive cDNA after surgery had worse DFS scores despite adjuvant chemotherapy. Patients with stage II CRC without ctDNA after surgery in 100 % did not have disease progression regardless of adjuvant CT.Conclusion. The presence of cDNA before and after surgery was a negative prognostic factor of progression after surgical treatment at stage I–III. The high negative prognostic value of cDNA makes it possible to select patients with stage II who do not need adjuvant chemotherapy.Введение. Исследования, посвященные неметастатическому колоректальному раку, продемонстрировали прогностическое значение анализа циркулирующей опухолевой ДНК (цоДНК) после операции, что в перспективе позволит персонализировать как неоадъювантное, так и адъювантное лечение.Цель исследования – изучить прогностическое значение статуса цоДНК до и после операции у пациентов с колоректальным раком I–III стадии.Материалы и методы. В исследование были включены данные пациентов с морфологически верифицированным колоректальным раком I–III стадии, проходивших лечение в Национальном медицинском исследовательском центре онкологии им. Н. Н. Блохина в период с 2016 по 2021 г. Забор образцов крови осуществлялся до и после хирургического лечения (на 7–10‑е сутки после операции). Минимально допустимая концентрация, при которой цоДНК в образце плазмы считали позитивной, – 0,4 копий мутантного ДНК в 1 мкл плазмы. Основным критерием эффективности являлась выживаемость без признаков болезни (ВБПБ).Результаты. В исследование были включены 146 пациентов с колоректальным раком I–III стадии. Прогрессирование выявлено у 34 больных. Медиана времени наблюдения составила 22 мес (1–66 мес). Данные о прогрессировании заболевания получены для 119 пациентов. Положительный цоДНК-статус до операции выявлен у 55 (45 %) из 120 больных, после хирургического вмешательства – у 46 (38,6 %) из 119. В группе цоДНК+ медиана ВБПБ до операции составила 35 мес (95 % доверительный интервал (ДИ) 24,0–45,9), в группе цоДНК она не была достигнута (отношение рисков (ОР) 4,6; 95 % ДИ 2,0–10,4). Однолетняя ВБПБ в группах положительного и отрицательного статуса цоДНК оказалась равна 62 и 100 % соответственно (p &lt;0,001). При цоДНК+ медиана ВБПБ после операции составила 20 мес (95 % ДИ 8,1–31,9), при цоДНК– она не была достигнута (ОР 27,7; 95 % ДИ 6,6–116,6; p &lt;0,001). Пациенты с положительным статусом цоДНК после операции имели худшие показатели ВБПБ, несмотря на проведение адъювантной химиотерапии. При колоректальном раке II стадии и отрицательном цоДНК-статусе после операции в 100 % случаев прогрессирования заболевания не наблюдалось (независимо от проведения адъювантной химиотерапии).Заключение. Наличие цоДНК до и после операции является негативным прогностическим фактором прогрессирования заболевания при колоректальном раке I–III стадии. Высокое негативное прогностическое значение цоДНК позволяет выбирать пациентов с заболеванием II стадии, не нуждающихся в проведении адъювантной химиотерапии