Kyiv Medical University

The aim is to examine the current state of development of microneedle systems for transdermal drug delivery. Materials and methods. Analysis, systematization, and generalization of data from scientific literature sources on the development of microneedle systems, research on their effectiveness, and prospects for use in pharmacy. A modified Arskey O'Malley methodology was used, refined by a research group led by H.M. Daudt. A total of 480 publications from the last ten years were analysed. Results. The results of the analysis show that most of the experimental studies focus on the development of microneedle systems for transdermal delivery of vaccines, insulin, and analgesics. In contrast, studies devoted to the creation of drugs with a different direction of action or drugs for the gradual release of active substances using microneedles occupy a smaller segment of the total number. Conclusions. It has been established that most scientists choose to develop microneedle-based drugs for systemic use. The main areas of publication are reviews of literature sources, the development of new microneedle systems, etc. The results obtained indicate the potential and relevance of conducting research on the development of microneedle systems

Recurrence after curative-intent resection remains common in intrahepatic cholangiocarcinoma (ICC) and continues to limit long-term survival. Although repeat liver resection may benefit carefully selected patients, this opportunity is often lost because recurrence is detected only after radiographic progression. Postoperative surveillance relies primarily on cross-sectional imaging, which performs well for macroscopic disease but lacks sensitivity for microscopic residual tumor. Consequently, relapse is frequently recognized only after structural visibility, when tumor biology may already be unfavorable. Minimal residual disease (MRD) represents the persistence of viable malignant cells below the threshold of radiographic detection and is increasingly implicated in early relapse. Circulating tumor DNA (ctDNA) analysis enables the detection of tumor-specific genomic alterations in peripheral blood and reflects active tumor biology rather than delayed anatomical change. Across solid tumors, ctDNA positivity has been associated with recurrence lead times of approximately 2-6 months before radiographic detection; however, ICC-specific prospective performance metrics, including sensitivity, specificity, and predictive values, remain limited and incompletely defined. Important practical challenges include assay variability, tumor shedding heterogeneity in biliary tract cancers, clonal hematopoiesis-related false positives, and uncertainty in managing isolated low-level molecular positivity. Accordingly, ctDNA should be considered a complementary rather than a replacement modality. This narrative review synthesizes current imaging and molecular evidence and proposes a hypothesis-generating hybrid imaging-molecular surveillance framework intended to guide future prospective validation rather than serve as an evidence-validated clinical algorithm.

Introduction. The problem of viral hepatitis C requires increased attention to studying the dynamics of morbidity in Ukraine, and comparison with global indicators contributes to identifying domestic epidemiological specifics and determining epidemiological factors of disease transmission, as well as developing and implementing preventive measures. Aim. Comprehensive epidemiological analysis of viral hepatitis C incidence in Ukraine for the period 2013–2023 compared with corresponding global indicators. Materials and methods. According to official statistical reports from the Public Health Center of the Ministry of Health of Ukraine and an analytical report by the Robert Koch Institute, the incidence of viral hepatitis C in Ukraine was analyzed for the period 2013-2023. A comparative analysis of viral hepatitis C incidence rates in Ukraine was conducted by comparing global data published by the WHO and the European Centre for Disease Prevention and Control. Results. An analysis of global viral hepatitis C prevalence rates has shown that the disease is prevalent in all WHO regions. The highest HCV prevalence rates are observed in the Eastern Mediterranean Region, where 12 million people are chronically infected. WHO analytical data on primary and chronic viral hepatitis incidence worldwide show a negative trend since 2019. During 2013-2022, there was a gradual decline in the total number of HCV cases: the number of acute forms of infection decreased by almost half, from 698 cases in 2013 to 397 in 2022; the number of chronic cases decreased from 6,144 in 2013 to 3,575 cases registered in 2022. In 2023, the epidemiological situation regarding HCV incidence significantly worsened: there was an increase in the total number of registered cases of both acute and chronic forms of the disease. The reason for the deterioration of the epidemiological situation is related to the full-scale Russian aggression in 2022, when the risk of infection with parenteral viral hepatitis increased significantly due to: injuries; contact with blood that had not undergone appropriate testing; injuries and sexual violence; deterioration of access to medical care due to the destruction of health care facilities; displacement of a significant number of people from the eastern and southern regions of Ukraine. According to global analytical forecasts, by 2030, preventive programs and measures against viral hepatitis C will lead to a significant reduction in both primary morbidity and mortality from the infection. Conclusions. Full-scale Russian aggression has negatively affected the incidence of viral hepatitis C in Ukraine. Improvements in the epidemiological situation regarding viral hepatitis C are possible due to increased effectiveness of non-specific prevention, implementation of the basic principles of the National Strategy for Combating HIV/AIDS, Tuberculosis, and Viral Hepatitis.

Background. Acute cerebrovascular accidents remain one of the leading causes of mortality and long-term disability. Current therapeutic approaches do not provide sufficient control of neuroinflammation, which necessitates the search for effective corrective strategies. A promising direction involves the use of mesenchymal stem cells (MSCs) in combination with antioxidants, particularly resveratrol, which potentiates the neuroprotective properties of MSCs. Aim: to investigate the dynamics of cytokine concentration changes during the acute and early recovery periods of experimental ischemic stroke under the influence of MSCs and their combination with resveratrol. Materials and methods. A model of focal cerebral ischemia was reproduced according to the E.Z. Longa et al. method (1989). Serum levels of pro-inflammatory (IL-1β, IL-6, TNF-α) and anti-inflammatory (IL-4, IL-10, TGF-β1) cytokines, as well as β-endorphin, were determined using ELISA. Animals were divided into three groups: no treatment, MSCs, and combined MSCs + resveratrol therapy. Corrective interventions were administered once daily. Results. MSC monotherapy produced a moderate decrease in pro- and partially anti-inflammatory cytokines during the acute and early recovery phases. Combined therapy resulted in a statistically significant and more pronounced reduction in IL-1β, IL-6, TNF-α, TGF-β1, and β-endorphin levels, indicating suppression of cytokine cascade hyperactivation and normalization of the immune microenvironment. Conclusion. Combined treatment with MSCs and resveratrol provides substantially greater attenuation of the neuroinflammatory response compared with monotherapy. The findings support the potential of a combined cell-based and antioxidant approach for limiting secondary ischemic damage and creating favorable conditions for neurorepair.

BACKGROUND. Vasomotor rhinitis represents a significant global health burden, with prevalence rates ranging from 5 to 25 %. It is a subtype of non-allergic rhinitis, a heterogeneous group of disorders characterized by rhinitis symptoms not caused by atopy or infection, which are sometimes grouped with other phenotypes such as gustatory, hormonal, or drug-induced rhinitis. In contrast to allergic rhinitis, which involves IgE-mediated immune responses, vasomotor rhinitis is driven by neurogenic and autonomic dysfunction. Previously, several authors proposed using the terms “vasomotor rhinitis” and “non-allergic rhinopathy” concurrently, or even classifying allergic rhinitis under vasomotor rhinitis. This creates discrepancies in interpreting the concepts of “vasomotor rhinitis”, “non-allergic rhinopathy”, and “allergic rhinitis”, hindering a clear understanding of management approaches for the respective patient categories. OBJECTIVE. To analyze available data on the etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of vasomotor rhinitis. MATERIALS AND METHODS. A search for available information sources, analytical processing, and discussion of the obtained results. RESULTS AND DISCUSSION. Vasomotor rhinitis is a common, yet poorly studied, type of chronic rhinitis that is currently believed to be neurogenic in origin. Several authors use the term “non-allergic rhinopathy” instead of “vasomotor rhinitis”, which complicates the understanding of this issue. Currently, there are no unified international diagnostic criteria for vasomotor rhinitis. In real clinical practice, physicians should perform differential diagnosis between vasomotor and allergic rhinitis (using specific allergodiagnostic methods), as well as exclude infectious rhinitis, drug-induced rhinitis, and chronic rhinosinusitis (using history taking, endoscopy, and other supplementary investigation methods). The majority of patients with vasomotor rhinitis respond adequately to treatment with topical saline solutions, topical antihistamines, corticosteroids, and ipratropium sprays, all of which alleviate rhinitis symptoms. Individuals who are refractory to traditional treatment may undergo therapy with capsaicin, botulinum toxin, and posterior nasal nerve ablation using radiofrequency ablation or cryotherapy. Currently, biological agents and neuromodulatory treatments are at various stages of investigation, focusing on the effect of such targeted therapy on type 2 inflammation, specifically the blockade of interleukin-4 and -13. Despite the encouraging nature of this data for other rhinitis subtypes, their role in vasomotor rhinitis remains unclear. Standardized and highly agreed-upon diagnostic criteria for vasomotor rhinitis must be developed to allow for more precise patient classification through phenotyping, enable targeted therapeutic selection, and establish a reliable evidence base regarding the efficacy and safety of treatment methods for this patient category. CONCLUSIONS. Patients with vasomotor rhinitis often seek medical attention from allergists, otolaryngologists, and physicians of other specialties. Currently, there is no standardized approach to the management of such patients among various specialists. The issue of vasomotor rhinitis remains relevant and poorly understood, but the approaches to managing these patients must be unified.

Calcifying nested stromal-epithelial tumor (CNSET) is an extremely rare primary liver tumor of uncertain histogenesis that predominantly occurs in the pediatric age group and young adults. Knowledge regarding the molecular genetic profile of this entity remains limited, with only two molecular studies conducted to date, which identified pathogenic mutations in the CTNNB1 gene and TERT promoter mutations in all analyzable cases. A more aggressive biological potential than previously reported has been only recently unveiled as well. To further advance the understanding of pathogenic mechanisms of CNSET and to investigate the distinctiveness of this rare entity, we analyzed two cases using immunohistochemistry, next-generation sequencing (NGS), and methylation profiling. The latter was employed to compare the epigenetic landscape of CNSET with that of clinicopathologically similar entities, such as hepatoblastoma and solid pseudopapillary neoplasm (SPN) of the pancreas. Both CNSET cases occurred in women (aged 24 and 23years) and measured 24cm and 16cm in diameter, respectively. Both cases showed similar histological features, being composed of organoid nests of bland spindled to epithelioid cells embedded in myofibroblastic stroma. Both cases were immunohistochemically positive for CD56, WT1, and CAM5.2 and negative for hepatocellular and neuroendocrine markers. Case 2 showed aberrant nuclear expression of β-catenin, while in case 1, there was cytoplasmic positivity only. Using Illumina TruSight Oncology 500 NGS panel, case 1 revealed a pathogenic mutation in the WT1 gene and a TERT promoter mutation, and case 2 had a CTNNB1 mutation. DNA methylation analysis showed that CNSET forms a distinct cluster, separate from other reference entities. Follow-up in case 2 revealed a disease-free status 21months after partial hepatectomy. This study showed that the molecular landscape of CNSET of the liver is characterized by CTNNB1, TERT promoter, and WT1 gene mutations, with the latter representing a novel alteration. Similarly to CTNNB1, the WT1 gene plays a significant role in the Wnt signaling pathway. Given the metastatic potential and chemotherapy resistance of CNSET, understanding its molecular background is important for potential alternative targeted treatment. Methylation profiling confirms CNSET as a distinct entity, separate from hepatoblastoma and SPN of the pancreas.

In this editorial, we analyze articles of the “Images” type in other peer-reviewed journals as well as the 6-year experience of publishing such articles in the Journal of Diagnostics and Treatment of Oral and Maxillofacial Pathology (JDTOMP). We also describe the experience of citing articles from the JDTOMP and The New England Journal of Medicine (NEJM) in the Scopus database. This is important for every peer-reviewed publication because one of the notes and conditions for indexing a journal in Scopus is citations of its articles in good journals indexed in Scopus. Taking into account the experience of journal in publishing 19 articles of the Images type, it was decided to expand the direction of publishing short manuscripts, but with a slightly different focus. A new section called “Images: Digital” has been launched, which aims to publish the same ultra-short articles, but not dedicated to pathology, but specifically dedicated to digital solutions in oral and maxillofacial surgery.

IntroductionLeukocyte telomere length is considered a promising prognostic marker associated with COVID-19 severity, adverse outcomes (hospital admission, need for critical care, and respiratory support), and mortality. However, the contribution of telomere length to post-COVID-19 syndrome (PCS) development is unclear.AimThis study aimed to evaluate the association between telomere shortening and the course of PCS in patients with type 2 diabetes (T2D) and to determine whether telomere length is linked to clinical phenotype, gender, and biological age.Materials and methodsIn this cross-sectional study, 66 T2D patients who had recovered from COVID-19 were enrolled. Patients were divided into two groups depending on PCS development: the PCS group (n = 44) and patients who did not develop PCS (n = 22) within 6 months after COVID-19 infection. Relative telomere length was determined using the standardized method proposed by Cawthon et al. A range of machine learning models was developed for PCS prediction. These models underwent training utilizing a cross-validation approach, as well as internal validation.ResultsWe observed a significantly lower mean of telomere length in T2D patients with PCS as compared to those without it (1.09 ± 0.19 and 1.28 ± 0.24; p = 0.001). In the sub-analysis, shorter telomeres were observed in female patients and patients of older age in both groups. The mean telomere length did not differ significantly among clinical phenotypes of PCS (p = 0.193). The best model generated for PCS prediction was the gradient boosting machine (GBM), which achieved an AUC of 0.753. The most influential variables across the top 10 models included telomere length, HbA1c, vitamin D3, waist circumference, ApoA1, C peptide, ApoB, COVID-19 severity, duration of T2D, IL-6, cholesterol, BMI, and age. Leukocyte telomere length and HbA1c exhibited significantly greater impact than other features.ConclusionShorter telomere length and higher HbA1c levels were significantly associated with the presence of PCS in our cohort of individuals with T2D. These factors may represent potential biomarkers that warrant further investigation.

Introduction and aim. Previously, we found the characteristics of desquamated endothelial cells circulating in the blood (CECs) in patients with diabetic angiopathy as well as stage II hypertension accompanied by ischemic heart disease. The literature on the effects of alcohol consumption on the cardiovascular system is mixed. Therefore, the aim of this study was to determine the characteristics of CECs in patients with hypertonic disease accompanied by alcoholism. Material and methods. The object of clinical observation was 38 patients of both sexes with stage II hypertension, which in 20 of them was accompanied by chronic alcoholism. The control group consisted of 21 healthy volunteers. The main subject of the study was the levels of blood pressure and CECs. In addition, routine general blood analysis performed and determined metabolic parameters in serum. Results. It was found that alcoholism is accompanied by minimal for the sample subnormal levels of markedly and terminally altered circulating endothelial cells (ACEC), LDLP cholesterol, triglycerides, prothrombin, Klimov’s and Dobiasova’s&Frolich’s atherogenity indices, ankle-brachial index of blood pressure (as atherogenity marker) as well as glucose, platelets and leukocytes. Instead, such patients have the maximum for the sample levels of HDLP cholesterol, erythrocytes sedimentation rate, body mass index, urea and creatinine. At the same time, the levels of hemoglobin, erythrocytes and cholesterol total as well as negentropy of endotheliocytogram and lipidogram did not differ from the controls, despite the presence of AH II. At the same time, both diastolic and systolic hypertension are less pronounced than in sober patients. Canonical correlation analysis showed that the absolute levels of the three fractions of CECs are determined by a constellation of 11 factors by 66,7%. Instead, the percentage and negetropy of CECs correlate with the registered factors much weaker (R2=0,390). The U-shape relationship between duration of alcohol consumption and number body parameters detected. Conclusion. Alcohol consumption by patients with arterial hypertension has a significant impact on a number of body parameters, the severity of which depends nonlinearly on the duration of alcoholism.

The article examines the global issue of the importance of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), which remains a serious public health challenge despite progress in prevention, treatment and care of this problem. HIV / AIDS continues to affect the lives of millions, with a particularly high prevalence in sub-Saharan Africa and increasing cases in Eastern Europe and Central Asia.The challenges that arise for the general practitioner – family medicine physician when managing patients with HIV / AIDS are presented. The article describes a clinical case of a patient with HIV / AIDS who gave birth to a healthy child. The example illustrates the visits to the family physician and discussion of problems associated with taking antiretroviral therapy, vaccination and treatment of concomitant diseases. The main challenges for the family doctor: combating stigma (the patient faced refusals to sign declarations), ensuring adherence to antiretroviral therapy – the woman stopped therapy due to misconceptions about side effects, organizing vaccinations (the patient was afraid of vaccinations because of HIV) and coordinating social support. The article emphasizes that antiretroviral therapy reduces the risk of HIV transmission from mother to child to 1%, which is confirmed by the patient’s case.The article also analyzes the factors that influence the prevalence of HIV / AIDS, including cultural stigma, access to health services and public policy. It describes how differences in social and economic conditions, access to preventive services and stigma affect the difference in infection rates between regions and the state of HIV / AIDS in Ukraine. It analyzes the reform of medicine in Ukraine, in which the family doctors play a key role in ensuring long-term care for patients. The role of family doctors in ensuring the longevity of patients with HIV / AIDS and the need for further education and support from government institutions are highlighted. The article shows the importance of a regional approach to overcome the HIV / AIDS epidemic and the role of family doctors in solving this global problem, focusing on the need to ensure access to treatment, the need for additional training for doctors, increased payment for working with such patients, and a comprehensive approach to reducing stigma and improving access to treatment.