Meshalkin National Medical Research Center

The use of artificial intelligence (AI) technologies in clinical trials (CT) of medicines has led to a significant reduction in time and financial costs for the development of new medicines. However, their widespread adoption faces a number of unresolved issues related to data quality, regulation, ethics, and security. The purpose of this study was to assess the current state of AI application in CT and identify key issues hindering its widespread adoption. Results and discussion . The key applications of AI in CT are analyzed: the use of large language models (TrialGPT, Elsa) for data analysis, the creation of digital patient counterparts and synthetic controls for CT modeling, as well as predictive analytics to optimize research design and risk assessment. It has been shown that these methods can improve the efficiency of patient selection, predict outcomes with a high area under ROC score (up to 92.7 %), and accelerate drug development. However, serious limitations have been identified: the dependence of the quality of models on the representativeness of data, the risks associated with imperfect algorithms, as well as the lack of specialized regulatory regulation and standards, including in the Russian Federation. The problems of data confidentiality, obtaining informed consent, and determining responsibility for harm caused by the use of AI are highlighted. Conclusions. The widespread use of AI to increase the efficiency and personalization of CT, its scaling requires solving complex regulatory, legal and ethical challenges.

Purpose: This study evaluates the impact of Civil Society Organizations (CSOs) in combating corruption in Uganda, examining their strategies, achieved outcomes, and the contextual factors influencing their effectiveness. Method: A qualitative research design was adopted. Data were collected through interviews with 58 purposively selected respondents drawn from CSOs, government agencies, and faith-based institutions engaged in anti-corruption initiatives. Thematic analysis was conducted using Atlas.ti software. Findings: The findings reveal that CSOs play a significant role through advocacy campaigns, monitoring of government programs, civic education, and follow-up on Auditor General recommendations. These interventions have contributed to increased public awareness and enhanced grassroots demand for accountability and improved service delivery. However, the persistence of high corruption levels indicates structural constraints, including limited political will, intimidation of CSO actors, bureaucratic resistance, selective enforcement of anti-corruption laws, and institutional fragility. Originality: Although legally recognized as partners in governance frameworks, CSOs operate within a politically restrictive environment that substantially limits their transformative impact. The study argues that CSO participation in anti-corruption efforts in Uganda often reflects institutional tokenism rather than genuine empowerment. The research contributes to broader debates on societal accountability, governance reforms, and the structural limits of civil society influence in corruption-prone environments.

To reconstruct the right ventricular outflow tract (RVOT) during the Ross procedure, various types of conduits are used. However, their application is often limited due to donor availability. A polytetrafluoroethylene (PTFE) valved conduit can be considered a viable alternative. This study summarizes 17 years of experience with RVOT reconstruction via polytetrafluoroethylene (PTFE)-valved conduits in adult patients who underwent the Ross procedure. To collect data, an extensive search of our clinic’s medical database was conducted. Follow-up data were collected either via phone calls or during in-person visits. Between 2007 and 2018, 20 adult patients (> 18 years old) who underwent RVOT reconstruction with PTFE valved conduits were retrospectively analysed. The mean patient age was 39.8 ± 14.3 years, and the mean follow-up period was 9.9 ± 3.5 years. Echocardiography was used to assess conduit function during follow-up. There was one early death and one late death. The mean conduit size was 25.3 ± 1.5 mm, and the mean peak RVOT gradient was 23.3 ± 11.7 mmHg. Mild or less regurgitation was observed in 7 patients (35%), moderate - in 2 patients (10%), with no cases of severe regurgitation observed. Freedom from conduit dysfunction at the latest follow-up was 90%. Conduit replacement was successfully performed in one patient. For RVOT reconstruction in adult patients undergoing the Ross procedure, a PTFE valved conduit is a feasible alternative without compromising surgical outcomes. Retrospectively registered.

Accurate and fast segmentation of magnetic resonance (MR) images with volumetric brain formations, such as glioblastomas and meningiomas, helps plan surgical and radiation treatment, increase the safety and radicality of surgical intervention, which in turn allows to increase the overall life expectancy of patients and the disease-free period. It is required for the development and evaluation of the effectiveness of a deep convolutional neural network with transmission connections for automatic segmentation of volumetric brain formations (meningiomas and glioblastomas) on postoperative MR images, as well as analysis of its accuracy in comparison with manual expert segmentation and existing methods. Material and methods . The paper considers the creation of an architecture inspired by the SegResNet model, training on BraTS2024-GLI and BraTS2024-MEN-RT, describes a method for compiling a training sample that reduces class imbalance, and analyzes the results in comparison with participants in the BraTS 2024 competition. Results and discussion . The developed model was trained and tested on two datasets of postoperative images of glioblastoma and meningioma. Several metrics are analyzed to compare the model with the methods described in the literature, as well as to evaluate it in the context of the variability of manual segmentation by different experts. The model achieves a Sorensen coefficient 0.8299 for meningioma segmentation and 0.7028 for glioblastoma contrast-accumulating region segmentation. In addition, the segmentation of the model provides an accurate estimate of the volume of the tumor area, as evidenced by the high values of the coefficient of intra-class correlation – 0.9661 for meningioma and 0.8339 for glioblastoma. Overall, the developed model requires fewer resources for learning and getting results. Conclusions. Model performs segmentation at least at the expert level, but with significantly less variability, especially when assessing the volume of the tumor after surgical treatment.

Relevance. Primary malignant neoplasms of bones and articular cartilage account for about 0.2% of all cancer cases and are characterized by an aggressive course, high tendency to metastasize, and resistance to therapy, which leads to unsatisfactory survival rates, especially at late stages. Existing diagnostic methods (visualization, biopsy) are associated with risks and have limitations, including the lack of specific immunohistochemical markers and insufficient sensitivity for early detection of these diseases. Objective. A review of the literature to assess the use of “liquid biopsy” based on blood exosomes for the diagnosis and monitoring of malignant neoplasms of bones and articular cartilage. Material and methods. The work used data from 46 articles devoted to the study of the composition and functions of exosomes, their role in the oncogenesis of malignant neoplasms of bones and articular cartilage, as well as the results of studies on the use of the molecular cargo of exosomes as a source of potential biomarkers. Results. It has been established that miR-25-3p has a high diagnostic potential for diagnosing osteosarcoma, miR-525 for chondrosarcoma, and miR-152 and miR-34a for Ewing’s sarcoma, which are involved in regulating the proliferative activity of tumor cells. Thus, analysis of exosome contents allows us to determine the tumor type, predict the response to therapy and the risk of metastasis, overcoming the limitations of traditional biopsy

The relationship between myocardial injury after cardiac surgery (MICS), ischemia on electrocardiogram (ECG), and mortality is uncertain. In this study we aimed to determine whether potential ischemic ECG changes after cardiac surgery are associated with 30-day mortality. In a cohort of adults who underwent cardiac surgery, experts interpreted ECGs preoperatively; on postoperative days 0, 1, 2, and 3; and on the last day before discharge (59,539 total ECGs reviewed) for new potential ischemic ECG changes. Among 12,594 patients, 9097 (72.2%) had potential ischemic ECG changes; 259 (2.1%) died within 30 days after surgery. Among patients with troponin elevation meeting MICS criteria, in models adjusting for EuroSCORE II, the hazard ratio (HR) for 30-day mortality was 0.57 (95% confidence interval [CI] 0.35-0.94, P = 0.03) for new Q waves, 2.17 (95% CI 1.14-4.13, P = 0.02) for ST depression ≥ 2 mm, and 0.58 (95% CI 0.39-0.87, P = 0.007) for T-wave inversion 1-1.9 mm. ST elevation was not significantly associated with 30-day mortality. The only ECG change for which coronary artery bypass grafting (CABG) was an effect modifier was new left bundle branch block (LBBB), with an HR of 2.78 (95% CI 1.69-4.60, P = 0.0001) with CABG and an HR of 1.10 (95% CI 0.54-2.21, P = 0.27) without CABG (P value for interaction = 0.03). After cardiac surgery, potential ischemic ECG changes are common and have divergent associations with mortality. ST depression was associated with a higher risk of death, whereas new Q waves and T-wave inversions were associated with a lower risk of death. A new LBBB was associated with a higher risk of death only among patients who underwent CABG. Potential ischemic ECG changes are common after cardiac surgery and lack specificity for the diagnosis of myocardial infarction.

Despite the development of modern technologies in the field of healthcare and the wide application of modern diagnostic and treatment methods, mortality from ischemic heart disease remains the leading cause of death among diseases. It is known that coronary artery bypass grafting in combination with optimal medical therapy is the gold standard for treating patients with multivessel coronary artery disease. However, for several decades now, percutaneous coronary intervention has proven to be an alternative method of myocardial revascularization for patient with multivessel coronary artery disease and low or intermediate risk. Nevertheless, despite accumulated experience in treating patients with ischemic heart disease, the choice of revascularization method for patients with complex coronary artery disease and high surgical risk (not eligible for CABG) remains debatable. In this review article, the authors described the main factors influencing the choice of myocardial revascularization strategy and demonstrated the results of clinical studies dedicated to studying this issue.

This report highlights the diagnostic challenges and successful surgical management in a symptomatic pediatric case with anomalous origin of the circumflex artery from the pulmonary artery. A 4-year-old boy presented emergently with dyspnea and substernal pain. Coronary angiography identified the circumflex artery originating anomalously from the right pulmonary artery. Emergency surgical reimplantation to the aorta was performed, with subsequent normalization of cardiac function (EF 67 % at 3-month follow-up). Although exceptionally rare, anomalous origin of the circumflex artery from the pulmonary artery requires high clinical suspicion in pediatric patients with ischemic symptoms. Early anatomical correction yields excellent outcomes, as demonstrated in this case.

BackgroundThe incompetence of the tricuspid valve (TV) may predispose to unfavorable results of Fontan palliation in patients with single right ventricle (RV). This study aims to reveal the effect of TV intervention in patients with single RV on long-term outcomes after Fontan completion.MethodsA single-center retrospective cohort study was conducted with patients who underwent Fontan completion from 1985 to 2017. There was a total of 678 patients with single RV. A total of 128 patients (18.8%) underwent TV intervention at any stage (TVI group); 30 of them (23.4%) underwent repeat TV surgery (repeat TVI subgroup). The control group comprises 550 patients (81.2%) who had no TV surgery regardless of the degree of TR (non TVI group).ResultsThe median follow-up was 8.8 (± 7.6) years. Overall transplant- and Fontan takedown-free survival was 62.5% (95% CI 59.2%-64.9%) at 20 years. The repeat TVI group had significantly lower transplant and takedown-free survival rates (Non TVI 76.5% vs. Single TVI 75.3% vs. repeat TVI 56.0% at 15 years, P = 0.02). The younger age at Fontan (1.12 [95% CI 1.02–1.22], p = 0.019), repeat TVI (3.33 [95% CI 1.57–7.04], p = 0.002), TV intervention after Fontan (6.14 [95% CI 2.60–14.50], p < 0.001), significant ventricular dysfunction before Fontan (3.12 [95% CI 1.12–8.30], p = 0.028) and any concomitant procedure at Fontan (1.98 [95% CI 1.16–3.37], p = 0.013) were the significant risk factors for transplant and takedown free- survival.ConclusionsRepeat TV intervention during the Fontan was associated with inferior outcomesin patients with morphologic systemic RV. Successful TV intervention could provide comparable long-term survival outcomes to non-TV intervention patients.

<title>Abstract</title> Patient-specific factors critically influence the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) for cardiac regeneration. In this work, we identify lymphocyte count as a key clinical predictor of BM-MSC proliferative capacity, with coronary artery disease significantly delaying expansion in patients undergoing cardiac surgery. Thus, we established cell selection criteria for patient-derived MSCs for further differentiation into cardiomyocytes. To overcome the limitations of MSCs in cardiac differentiation, we developed a novel protocol using conditioned medium mimicking patient-specific in vivo conditions from iPSC-derived cardiomyocytes (iPSC-CM). This approach successfully generated functional cardiomyocytes from patient-specific BM-MSCs, as evidenced by spontaneous calcium transitions, structural maturation, and electrophysiological activity. Our results provide a unique protocol for inducing MSC differentiation for cell therapy from patient selection to patient-specific personalized preparation as a differentiation strategy.