Geriatric syndromes (GSs) and aging-associated diseases (AADs) are common side effects of aging. They are affecting the lives of millions of older adults and placing immense pressure on healthcare systems and economies worldwide. It is imperative to study the factors causing these conditions and develop a holistic framework for their management. The so-called long-lived individuals—people over the age of 90 who managed to retain much of their health and functionality—could be holding the key to understanding these factors and their health implications. We analyzed the health status and lifestyle of the long-lived individuals and identified risk factors for GSs. Family history greatly contributes to the health and prevention of cognitive decline in older adults. Lifestyle and certain socioeconomic factors such as education, the age of starting to work and retiring, job type and income level, physical activity, and hobby were also associated with certain GSs. Moreover, the levels of total protein, albumin, alpha-1 globulins, high-density lipoprotein, free triiodothyronine, and 25-hydroxyvitamin D were direct indicators of the current health status. The proposed mathematical model allows the prediction of successful aging based on family history, social and economic factors, and life-long physical activity (f1 score = 0.72, AUC = 0.68, precision = 0.83 and recall = 0.64).

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and β-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.

INTRODUCTION: The main goals of treatment of superficial thrombophlebitis of lower limbs (ST LL) can be achieved using different treatment tactics: conservative treatment, surgical intervention, and their combination. AIM: To perform a comparative analysis of the effectiveness of pharmacotherapy, crossectomy in combination with pharmacotherapy and of phlebectomy in combination with pharmacotherapy in patients with ST LL. MATERIALS AND METHODS: A comparative analysis of the effectiveness of the therapeutic tactics of ST LL was conducted (86 patients; 36 men and 50 women). Group 1 patients received only conservative treatment, group 2 patients underwent crossectomy and conservative treatment in the postoperative period, group 3 — phlebectomy in combination with conservative treatment. The clinical effectiveness of treatment was evaluated by the recurrence rate and/or progression of the disease within 3 months after treatment and the level of life quality (Chronic Venous Insufficiency Questionnaire, CIVIQ 20, visual analog scale, VAS). Based on the data obtained in the study, a mathematical model was developed to determine the maximally effective treatment method. For mathematical modeling, a ‘random forest’ method was used. RESULTS: All the studied treatment methods demonstrated a comparative clinical effectiveness. Analysis of the dynamics of the studied parameters (adjusted for gender and age of the patients) compared with their initial values within each group showed that statistically significant changes in the psychological factor were observed in the pharmacotherapy group already on the 7th control day (p = 0.024), while in the crossectomy and phlebectomy groups only on the 14th day. In the groups of pharmacotherapy (p = 0.001) and phlebectomy (p = 0.005), the improvement in terms of the social factor occurred faster than in the group of crossectomy, since statistically significant differences were found on the 7th day, and in the group of crossectomy only on the 14th day. CONCLUSION: All the groups demonstrated comparable clinical effectiveness in normalization of the quality of life and the recurrence rate and/or progression of the disease within three months after completion of treatment. On the basis of the data obtained, predictive models have been constructed that allow, based on the initial characteristics of the patient, to determine the tactics of therapy that can ensure maximum effectiveness in terms of normalization of values, reflecting the quality of life and VAS parameter.

Introduction. Currently in routine clinical practice, standard methods based on polymerase chain reaction (PCR) and immunohistochemical examination are used to determine microsatellite instability (MSI) and deficient mismatch repair system (dMMR). MSI identification using high-throughput sequencing (next generation sequencing, NGS) is of special interest because it allows to analyze a large number of microsatellites and simultaneously study alterations in therapeutically significant genes.Aim. To validate of amplicon-based NGS panel for analysis of MSI and alterations in clinically significant genes in colorectal cancer.Materials and methods. High-throughput sequencing for MSI analysis was performed on formalin-fixed paraffinembedded (FFPE) samples from patients with colorectal cancer of any stage using amplicon-based panel “Solo-test Driver” (Russia) which covers 38 genes and 39 short tandem repeats (mononucleotides). As a reference method, 5-loci (BAT25, BAT26, NR21, NR24 and NR27) PCR was used. In NGS, MSI was evaluated based on κmer distribution. Statistical analysis was performed using Cohen’s kappa (κ), Mann-Whitney u test, and Fisher’s exact test.Results. An amplicon-based NGS panel for analysis of MSI in 39 loci and alterations in 39 genes was developed and validated on 160 archival FFPE samples of colorectal cancer. Per PCR, 42 (26.25 %) samples were MSI-positive, 118 (73.75 %) were MSI-negative. The results of PCR and NGS were concordant in 98.75 % (158/160) cases.Conclusion. The κ coefficient was 0.97 which demonstrates high concordance of MSI analyses using PCR and the developed NGS-based assay system.

Введение. В настоящее время для отбора пациентов, которым может быть показана терапия анти-EGFR моноклональными антителами при метастатическом колоректальном раке (мКРР), применяют анализ мутаций в генах KRAS, NRAS, BRAF p.V600, а также микросателлитной нестабильности (MSI) и амплификации HER2 (ERBB2). Однако данные исследований Valentino и PARADIGM показывают, что проведение мультигенного NGS исследования и более строгий отбор пациентов с учетом молекулярного профиля опухоли позволяют точнее прогнозировать эффективность анти-EGFR терапии. Цель. Оценка встречаемости мутаций, потенциально ассоциированных с резистентностью к анти-EGFR терапии (мутации гиперселекции), у пациентов с левосторонним RAS/BRAF-отрицательным мКРР, включенных в проспективное исследование, и сравнение с ретроспективной выборкой. Материалы и методы. В проспективное клиническое исследование III фазы (NCT06226857) были включены пациенты с морфологически подтвержденным левосторонним мКРР с отсутствием активирующих мутаций в генах KRAS/NRAS/BRAF p.V600 по результатам ПЦР-тестирования. FFPE-образцы, полученные до начала терапии, были проанализированы с использованием тест-системы Соло-тест Драйвер (38 генов + MSI) на основе NGS. По результатам NGS тестирования, в зависимости от наличия нарушений в генах гиперселекции (HSG) пациенты были определены в соответствующую группу терапии. Также произведено сравнение данных с проведенным ранее ретроспективным NGS анализом. Исследование зарегистрировано в базе данных клинических исследований ClinicalTrials.gov (NCT06226857). Результаты. На момент публикации проанализированы 134 образца с использованием NGS. Суммарно 31 (23,1 %) пациент был определен как HSG+. Наиболее частыми нарушениями стали генетические варианты в генах TP53 (77,6 %), PIK3CA (12,7 %) и KRAS (11,2 %). В 24 (18 %) образцах были выявлены клинически значимые варианты в генах KRAS, NRAS или BRAF. Полученные результаты по частоте встречаемости отдельных биомаркеров статистически значимо не различались по сравнению с ретроспективной выборкой, за исключением данных по RAS/BRAF p.V600, что может быть связано с различиями в методологии скрининга пациентов. Выводы. Полученные с помощью NGS результаты проспективного исследования продемонстрировали высокую (18 %) встречаемость биомаркеров потенциальной первичной резистентности к анти-EGFR терапии. Чаще всего резистентность была обусловлена наличием редких мутаций в генах RAS, реже — альтерациями помимо RAS/BRAF p.V600.