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A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures.
(Diagnostics (Basel), 2023-05-25) Dosenko, Viktor; Dons’koi, Boris; Baksheev, Serhiy
Aim: NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. Methods: In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th-7th week of gestation-w.g.) and 66 women in the 11th-13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. Results: A misbalance in the NKp46+NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46high cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46hightCD56++) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Conclusions: Our results showed that accentuated levels of NKp46+NK cells lead to a negative prognosis for early pregnancy courses in women.
A minority of cases of acinic cell carcinoma of the salivary glands are driven by an NR4A2 rearrangement: the diagnostic utility of the assessment of NR4A2 and NR4A3 alterations in salivary gland tumors.
(Virchows Archiv, 2022-12-05) Koshyk, Olena; Klubíčková, Natálie; Grossmann, Petr; Šteiner, Petr
Acinic cell carcinoma (AciCC) is a common salivary gland malignancy, typically composed of neoplastic acinic cells with zymogen granules. The vast majority of cases are driven by a t(4;9)(q13;q31) leading to enhancer hijacking and upregulation of the NR4A3 gene. However, a minority of cases do not display NR4A3 overexpression on immunohistochemical examination and are negative for the rearrangement involving the NR4A3 gene when tested by FISH. Such cases overexpress NR4A2, and the protein product is detectable by immunohistochemistry. In this study, we aimed to assess the utility of NR4A2 and NR4A3 immunohistochemistry in the differential diagnosis of salivary gland tumors. Eighty-five cases of classic low-grade ACiCC, as well as 36 cases with high-grade transformation (HGT) and 7 high-grade AciCC cases were included in the analysis. NR4A3 was at least focally positive in 105/128 (82%) cases. Out of the 23 cases that were immunohistochemically negative for NR4A3, 6 displayed nuclear immunopositivity with the NR4A2 antibody. The NR4A3 rearrangement was confirmed by FISH in 38/52 (73%) cases. In addition, this is the first report of an NR4A2 rearrangement being detected by FISH in 2 AciCC cases that were negative for the NR4A3 rearrangement. Our analysis confirms that the majority of AciCC, including high-grade cases and cases with HGT, are immunopositive for NR4A3, and suggests that NR4A3 immunohistochemistry is a powerful tool in the differential diagnosis of salivary gland tumors. However, its utility is limited in sub-optimally fixed samples which often display weaker and focal positivity. Our study also indicates that in a minority of cases, AciCC might be negative for NR4A3 immunostaining, because the pathogenic genetic event in these cases is instead a rearrangement involving the NR4A2 gene.
Adjusting Laboratory Practices to the Challenges of Wartime
(Narrative Inquiry in Bioethics, 2023) Sulaieva, Oksana; Shcherbakova, Anna; Dudin, Oleksandr
After 500 days of the unjust war initiated by the Russians, we look back to reflect on the challenges our medical laboratory faced during these early days. On the morning of February 24th, we were awakened by the dreadful roar of sirens, the sound of which filled us with adrenaline and anxiety. Although our team had considered the risks of Russian military aggression and thus updated our emergency plan at the beginning of 2022, the first day of the war revealed that nobody was truly ready for the bombing, air alarms, tanks on the streets of towns and cities, violence and murders of civilians. That morning the city’s transportation system collapsed, and the flow of cars cluttered all the roads as people were trying to leave the city and escape the upcoming atrocities and death. Serious and disquieted people hurried along the streets—some people rushed to shelters, and others went to the military registration and enlistment offices to fight against Russian aggressors for the life, independence, and sovereignty of Ukraine. We hurried to work, committed to performing our duties. Our medical laboratory serves more than 750 hospitals in Ukraine. Despite fear and uncertainty, we walked to the lab, taking our children and alarm case1 with documents and essential things. Months later, people asked us why we went to the laboratory instead of leaving the city or even the country. At that moment, our [End Page 155] professional duties were an anchor linking us to each other against fear and panic. Our responsibility to provide patients and physicians with the results of blood testing, pathology, and molecular reports outweighed our fears of the war. We had to complete the testing of all the samples delivered to the laboratory to provide our customers—who include children, pregnant women, diabetic and cancer patients—with data essential for identifying accurate diagnoses and effective treatments. So we spent the first days of the war in the laboratory. At the same time, we had obligations and responsibilities to our staff as well. We had to consider how to manage our employees’ protection along with continuous laboratory services provided under endless air alarms and bombings. Many healthcare facilities in eastern regions and around Kyiv were affected by missiles or completely destroyed. Of our sixty laboratory offices around Ukraine, ten were damaged or abandoned due to occupation. Several of our fleet cars were also damaged and riddled with bullets. Many employees in the regional offices in Melitopol, Kherson, Mariupol, Chernihiv, and in suburbs of Kyiv such as Bucha and Irpin lost their homes as a result of massive military operations or occupation. Dozens of our employees joined the Ukrainian armed forces to defend civilians and fight against aggressors. Many others became volunteers, involved in blood donation, medical care for the wounded, cooking, and serving the troops. And still, we had to continue our work and protect our staff at the same time. We also helped each other by sharing our goods, medication, homes, cars, warmth, and support. Some pathologists stayed at the workplace for several days moving between pathology stations, microscopes and shelters, and sleeping on the floor but continuing to work. Our main challenge was the regular terroristic attacks on healthcare facilities situated far away from the front line, which in fact, violated international humanitarian law regarding respect for human rights during armed conflicts. During the first weeks of the war, the magnitude of military aggression, massive bombing, and air attacks undermined the healthcare system and endangered laboratory staff and patients. We prioritized protective measures. Some of our laboratory staff and facilities were evacuated from Kyiv to Lviv in western Ukraine. The partial relocation of our laboratory to Lviv was also driven by the displacement of several million Ukrainians to the western part of the country.
Alpha-methyl CoA racemase (AMACR) reactivity across the spectrum of clear cell renal cell neoplasms
(Annals of Diagnostic Pathology, 2024-03-24) Slisarenko, Maryna; Rotterova, Pavla; Alaghehbandan, Reza
a-Methylacyl coenzyme A racemase (AMACR) is traditionally considered to be a marker of papillary renal cell carcinoma. However, AMACR expression can be seen in other renal tumors. The aim of this study was to investigate AMACR immunoreactivity within the spectrum of clear cell renal cell neoplasms. Fifty-three clear cell renal epithelial tumors were used in assembling the following four cohorts: low grade (LG) clear cell renal cell carcinoma (CCRCC), high grade (HG) CCRCC, CCRCC with cystic changes, and multilocular cystic renal neoplasm of low malignant potential (MCRNLMP). Representative blocks were stained for AMACR, using two different clones (SP52 and OV-TL12/30). There were at least some AMACR immunoreactivity in 77.8 % and 68.9 % of CCRCCs (using SP52 and OV-TL12/30 clone, respectively). Moderate to strong positivity, or positivity in more than one third of the tumor (even weak in intensity) was detected in 46.7 % of CCRCCs using SP52 and in 48.9 % of CCRCC using OV-TL12/30 clone. The highest AMACR reactivity was observed in HG CCRCC (60 % by SP52 and 66.7 % by OV-TL12/30). Strong and diffuse AMACR positivity was detected in 8.9 % of all CCRCCs. AMACR immunoreactivity in MCRNLMP was 37.5 % (SP52 clone) and 25 % (OV-TL12/30 clone). We demonstrated relatively high expression rate of AMACR in CCRCC, while very variable in intensity and distribution. This finding may have diagnostic implications especially in limited samples (i.e., core biopsies), as AMACR positivity does not exclude the diagnosis of CCRCC.
Analysis of Sources of Funding for Compulsory Health Insurance
(2023-11) Olena Baieva; Olha Kovalenko
BIOETHICAL PRICIPLES OF MEDICAL CARE: INFORMED CONSENT TO TREATMENT
(2021-10-24) Baieva Olena; Zelentsova Svitlana; Kovalenko Olha
The article dealth with ethical and legal significance of the patient's consent to medical care is recognized by the fact that it acts as a tool for protecting the human right to self-determination, which is recognized as one of the basic human rights
BIOETHICS EDUCATION OF FUTURE DOCTORS DURING PRECLINICAL STAGE OF STUDY
(2021-11-12) Zelentsova Svitlana Mikolaivna,; Kovalenko Olha Oleksandrivna
The article deals with the main issues of teaching Bioethics in medical university. The importance of study bioethics during preclinical stage expounds in it. Justify the needs for an early stage in the formation of bioethical consciousness of future doctors
Biphenotypic sinonasal sarcoma with PAX3::MAML3 fusion transforming into high-grade rhabdomyosarcoma: report of an emerging rare phenomenonю
(Virchows Archiv, 2023-01-31) Koshyk, Olena; Meyer, Anders; Klubíčková, Natálie; Mosaieby, Elaheh
We report a case of a 67-year-old male patient with a sinonasal tumor that showed areas of classic biphenotypic sinonasal sarcoma (BSNS) which in some sections sharply transitioned into high-grade rhabdomyosarcoma. Immunohistochemically, the conventional BSNS parts showed S100 protein, SMA, PAX7, and focal MyoD1 expression, whereas desmin and myogenin were negative. In contrast, the cells in high-grade areas expressed desmin, MyoD1, myogenin, and PAX7, while being negative for S100 protein and SMA. Using the Archer FusionPlex assay, the classical PAX3::MAML3 gene fusion was detected. FISH for PAX3 and MAML3 confirmed a break of these genes in both components. Despite aggressive therapy, the tumor progression resulted in the patient's death. The herein presented case, together with 2 previously published cases of BSNS with high-grade transformation, helps to better understand this novel phenomenon. Although the risk for such transformation appears low, it has important clinical and diagnostic implications which are discussed.
Clear cell renal cell carcinoma with prominent microvascular hyperplasia: Morphologic, immunohistochemical and molecular-genetic analysis of 7 sporadic cases.
(Annals of Diagnostic Pathology, 2022-02) Slisarenko, Maryna; Alaghehbandan, Reza; Limani, Rinë; Ali, Leila
Clear cell renal cell carcinoma (CCRCC) is well known for intratumor heterogeneity. An accurate mapping of the tumor is crucial for assessing prognosis, and perhaps this can be linked to potential success/failure of targeted therapies. We assembled a cohort of 7 CCRCCs with prominent vasculature and microvascular hyperplasia (ccRCCPV), resembling those seen in high grade gliomas. A control group of classic CCRCC with no variant morphologies was also included. Both groups were analyzed for clinicopathologic, morphologic, immunohistochemical, and molecular genetic features. No statistically significant differences in mRNA expression of studied genes between the two groups were found. Using NGS panel Trusight Oncology 500 (TSO500), only one clinically significant gene mutation, VHL c.263G > A, p. (Trp88Ter), was found. TMB (Tumor Mutation Burden) and MSI (MicroSatellite Instability) were low, and no copy number variations (CNVs) were detected in the study cohort. Prominent microvascular hyperplasia in CCRCC is a rare phenomenon. From molecular genetic point of view, these tumors do not appear to be different from classic CCRCC. Prognostically, they also demonstrated similar clinical behaviors.
Combined effects of probiotic and chondroprotector during osteoarthritis in rats.
(Panminerva Medica, 2020-06) Sulaieva, Oksana; Korotkyi, Oleksandr; Dvorshchenko, Kateryna; Falalyeyeva, Tetyana
Background: Osteoarthritis (OA) is a joint affection, defined by articular cartilage demolition, risks of which rise with age. The aim of this study was to compare the efficacy of chondroitin sulfate (CS) course and multistrain live probiotic (LP) administered alone or in combination on the expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane during OA in rats. Methods: OA was induced in male rats by injecting monoiodoacetate (MIA) in right hind knee. Therapeutic groups received 3 mg/kg of chondroprotector (ChP) CS for 28 days and/or 140 mg/kg of LP diet for 14 days. The expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane were determined with immunohistochemical staining kits (Thermo Fisher Scientific). Results: It was established that MIA injection is associated with long-term structural changes in joint tissues that corresponded to OA-like features and associated with activation of pathogen-recognizing molecules and proinflammatory signaling pathways expression. Separate therapy with ChP and probiotics slightly decreased OA score limiting cell death and subchondral bone resorption. However, these changes were not associated with a significant decrease in TLR-2, TLR-4, NF-kB and TNF-α expression. On the other hand, the combination of ChP and LP treatment significantly decreased OA score. This correlated with a decrease in TLR-2, TLR-4, NF-kB and TNF-α expression in chondrocytes and synovial cells. Conclusions: The outcomes of our research prove that ChPs amplify the positive action of LPs in OA attenuation.
Complementary Effect of Non-Persistent Silver Nano-Architectures and Chlorhexidine on Infected Wound Healing.
(Biomedicines, 2021-09-14) Sulaieva, Oksana; Pernakov, Mykola; Ermini, Maria Laura
Surgical site infection (SSI) substantially contributes each year to patients' morbidity and mortality, accounting for about 15% of all nosocomial infections. SSI drastically increases the rehab stint and expenses while jeopardizing health outcomes. Besides prevention, the treatment regime relies on an adequate antibiotic therapy. On the other hand, resistant bacterial strains have currently reached up to 34.3% of the total infections, and this percentage grows annually, reducing the efficacy of the common treatment schemes. Thus, new antibacterial strategies are urgently demanded. Here, we demonstrated in rats the effectiveness of non-persistent silver nano-architectures (AgNAs) in infected wound healing together with their synergistic action in combination with chlorhexidine. Besides the in vivo efficacy evaluation, we performed analysis of the bacteriological profile of purulent wound, histological evaluations, and macrophages polarization quantifications to further validate our findings and elucidate the possible mechanisms of AgNAs action on wound healing. These findings open the way for the composition of robust multifunctional nanoplatforms for the translation of safe and efficient topical treatments of SSI.
Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations.
(Wiley Online Library. The Journal of Pathology., 2024-02-09) Koshyk, Olena; Klubíčková, Natálie; Dermawan, Josephine K; Mosaieby, Elaheh
Alterations in kinase genes such as NTRK1/2/3, RET, and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity 'NTRK-rearranged spindle cell neoplasms' included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene-altered spindle cell neoplasms affecting both pediatric and adult patients. Follow-up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months). Six patients were treated with targeted therapy, achieving a partial or complete response in five cases. Overall, three cases recurred and one metastasized. Eight patients were free of disease, five were alive with disease, and two patients died. All cases showed previously reported morphological patterns. Based on the cellularity and level of atypia, cases were divided into three morphological grade groups. S100 protein and CD34 were at least focally positive in 12/22 and 14/22 cases, respectively. Novel PWWP2A::RET, NUMA1::RET, ITSN1::RAF1, and CAPZA2::MET fusions, which we report herein in mesenchymal tumors for the first time, were detected by RNA sequencing. Additionally, the first uterine case with BRAF and EGFR mutations and CD34 and S100 co-expression is described. DNA sequencing performed in 13 cases uncovered very rare additional genetic aberrations. The CNV profiles showed that high-grade tumors demonstrate a significantly higher percentage of copy number gains and losses across the genome compared with low- and intermediate-grade tumors. Unsupervised clustering of the tumors' methylation profiles revealed that in 8/9 cases, the methylation profiles clustered with the IFS methylation class, irrespective of their clinicopathological or molecular features.
CONCEPTUAL FRAMEWORK FOR STANDARTIZATION OF MEDICAL CARE: PURPOSE AND PRINCIPLES
(2024-12) Baieva O.; Kryvenko Y.; Tarasova N.
The purpose of health care standardization is to improve the quality of preventive and therapeutic and diagnostic measures, solve the problems of preserving and improving the health of the population. Standardization of care seeks to improve patient outcomes and healthcare delivery by reducing unwanted variations in care as well as promoting the efficient and effective use of healthcare resources.
Conceptual principles for reforming the quality management system of medical care in Ukraine
(Primedia eLaunch, 2023) Baieva O.; Kovalenko O.; Zelentsova S.; Kryvenko Y.; Svizhak V.
This section of the monograph outlines a comprehensive framework for enhancing the quality management system in the Ukrainian healthcare sector. It identifies key challenges and opportunities for reform, emphasizing the need for integrated approaches that align with international best practices. The section discusses essential components such as stakeholder engagement, regulatory improvements, and the adoption of evidence-based methodologies. Recommendations are provided to guide policymakers and healthcare leaders in implementing effective reforms aimed at achieving higher standards of medical care in Ukraine
COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.
(Cancer Cytopathology, 2022-01-10) Sulaieva, Oksana; Vigliar, Elena; Pisapia, Pasquale; Iacovo, Filippo Dello
Background: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). Methods: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). Conclusions: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.
Digital Marketing as an Innovative Communication Tool in the Health Tourism System
(2020-08) Baiev V. V.; Baieva O. V.; Bakhov I. S.; Antonenko I. Y.; Melnyk I. L.
The article examines the essence of internet marketing and digital marketing in the context of their role in the system of integrated marketing communications in the field of health tourism. The leading sites of companies working in the field of health tourism are analyzed. The use of modern digital marketing technologies, in particular crowd marketing and its basic tools in the field of health tourism, is investigated
Digital pathology implementation in cancer diagnostics: towards informed decision-making.
(Frontiers in Digital Health, 2024-05-30) Sulaieva, Oksana; Dudin, Oleksandr; Koshyk, Olena; Panko, Mariia
Digital pathology (DP) has become a part of the cancer healthcare system, creating additional value for cancer patients. DP implementation in clinical practice provides plenty of benefits but also harbors hidden ethical challenges affecting physician-patient relationships. This paper addresses the ethical obligation to transform the physician-patient relationship for informed and responsible decision-making when using artificial intelligence (AI)-based tools for cancer diagnostics. DP application allows to improve the performance of the Human-AI Team shifting focus from AI challenges towards the Augmented Human Intelligence (AHI) benefits. AHI enhances analytical sensitivity and empowers pathologists to deliver accurate diagnoses and assess predictive biomarkers for further personalized treatment of cancer patients. At the same time, patients' right to know about using AI tools, their accuracy, strengths and limitations, measures for privacy protection, acceptance of privacy concerns and legal protection defines the duty of physicians to provide the relevant information about AHI-based solutions to patients and the community for building transparency, understanding and trust, respecting patients' autonomy and empowering informed decision-making in oncology.
Epidemiological and preventive aspects of Hepatitis C virus infection in Ukraine
(Boston: Primedia eLaunch, 2020) Baieva O.; Kovalenko O.; Tserkovniak L.; Slobodyan A.
Viral hepatitis is a common and dangerous infectious disease caused by various hepatitis viruses, which primarily affect human liver cells. Hepatitis C is a liver disease caused by the hepatitis C virus (HCV): the virus can cause both acute and chronic hepatitis, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness. Analysis of materials obtained in of the official registration of cases of the Ministry of Health of Ukraine, a total of 44359 cases of HCV infection were registered in country for 7 years (2013 - 2019), including 3826 cases of Acute hepatitis C - (8 , 44 ± 0.48)% and 41483 Chronic hepatitis C - (91.56 ± 0.48)%
ETHICAL AND LEGAL PRINCIPLES OF ORGANIZATION’S MEDICAL CARE TO POPULATION IN THE CONDITIONS OF COVID-19 PANDEMIC
(2021-02-05) Baieva Olena Viktorivna; Zelentsova Svitlana Mikolaivna; Kovalenko Olga Olexandrivna
The article dealth with mass vaccinations against COVID-19 may raise the bioethical dilemma of ensuring the patient's right to informed consent to medical intervention, on the one hand, and the right of citizens to health and a safe environment, on the other
Ethical navigation of biobanking establishment in Ukraine: learning from the experience of developing countries.
(Journal of medical ethics, 2023-11-09) Sulaieva, Oksana; Artamonova, Oksana; Dudin, Oleksandr
Building a biobank network in developing countries is essential to foster genomic research and precision medicine for patients’ benefit. However, there are serious barriers to establishing biobanks in low-income and middle-income countries (LMICs), including Ukraine. Here, we outline key barriers and essential milestones for the successful expansion of biobanks, genomic research and personalised medicine in Ukraine, drawing from the experience of other LMICs. A lack of legal and ethical governance in conjunction with limited awareness about biobanking and community distrust are the principal threats to establishing biobanks. The experiences of LMICs suggest that Ukraine urgently needs national guidelines covering ethical and legal aspects of biospecimen-related research. National guidelines must be consistent with international ethical recommendations for safeguarding participants’ rights, welfare and privacy. Additionally, efforts to educate and engage physicians and patient communities are essential for achieving biobanking goals and benefits for precision medicine and future patients.

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