Vitkauskienė, Astra
Item type:Publication, [Arilo angliavandenilių receptoriaus reikšmė kasos latakų adenokarcinomai: chemoterapinio atsparumo mechanizmai, mezenchiminė epitelio transformacija ir citoprotekcija]doctoral thesis[2026][N010][106]; ; ; ; ; ; ; Disertacijoje išsamiai tiriamas arilo angliavandenilių receptoriaus (AHR) vaidmuo ir klinikinė reikšmė kasos latakų adenokarcinomoje (PDAC). Pagrindinis tyrimo tikslas – kompleksiškai išsiaiškinti AHR įtaką chemoterapiniam atsparumui gemcitabinui per ELAVL1/DCK reguliacinę ašį, naviko agresyvumui per epitelio-mezenchiminę transformaciją (EMT) bei citoprotekciniams ir uždegiminiams signaliniams keliams (PTGS2/HO-1/PGE2). Naudojant pacientų audinių ir in vitro ląstelių modelių analizę, tyrime nustatyta, kad padidėjusi AHR raiška glaudžiai koreliuoja su limfmazgių invazija, blogesniais klinikiniais rodikliais bei ELAVL1, DCK, EMT ir citoprotekcinių žymenų kaita. Eksperimentiniai rezultatai atskleidė, kad AHR slopinimas arba genų nutildymas skatina apsauginio RNR surišančio baltymo ELAVL1 translokaciją į citoplazmą, padidina fermento DCK raišką ir sustiprina ląstelių jautrumą gemcitabinui. Kartu nustatyta, kad AHR moduliacija efektyviai mažina ląstelių migraciją, invaziją bei uždegiminio mediatoriaus PGE2 gamybą. Apibendrinant disertaciją, AHR veikia kaip centrinis PDAC progresavimo ir terapinio atsparumo reguliatorius, sudarantis prielaidas kurti naujas individualizuotas gydymo strategijas.
5 Item type:Publication, conference output[2026][T2][N010,M001][1]; ; ; ; 28th Annual Conference of the European Society for Clinical Virology ESCV 2026 : 16-19 September, Porto, Portugal : Abstract book, 2026-09-16, p. 131-131Introduction: Previous studies of post COVID-19 disease show that neutrophil extracellular traps (NETs) have ability to persist after SARS-CoV-2 infection. NETs clearance is important for the balance between NETs formation and degradation and plays a crucial role in tissue homeostasis. Recent studies have shown that endonucleases known as DNases are particularly important for the regulation of NETs by degrading the extracellular DNA that forms the basis of this structure to prevent excessive inflammatory reactions. This study aimed to explore the association between DNASE1 polymorphism and NETs formation in STEMI patients with previous SARS- -CoV-2 infection. Material and Methods: Patients’ blood and plasma samples were used in this study. Patients with acute MI (AMI) and with a history of COVID-19 disease were enrolled in the experimental group. The control group comprised patients who had previously tested negative for COVID-19 disease. Single-nucleotide polymorphism (SNP) of the DNASE1 (rs1053874) was evaluated using real-time PCR with TaqMan® SNP Genotyping Assay. Quantitative ELISA method and quantitative fluorescence spectroscopy method was used to measure the concentration of NET biomarkers. The difference was considered statistically significant at the value of P < 0.05. Results: Slow metabolizing allele G of DNASE1 was more frequent (P = 0.022) in the patients with STEMI after COVID-19 compared with control group. Univariate logistic regression analysis revealed that platelets count (P = 0.025), dsDNA count (P < 0.001), GG genotype (P < 0.004), and high NETs level (vs lower) were significantly associated with higher odds of prior COVID-19 among STEMI patients, meanwhile MPO (P = 0.025) and GA or AA (P = 0.025) genotype were associated with decreased odds. Conclusions: The DNASE1 and NETs level interaction analyses show that NETs burden may depend on DNASE1 genotype and could be associated with odds of previous SARS-CoV-2 infection among STEMI patients.
1 Item type:Publication, [Naujojo Hb/kg indekso svarba vertinant perioperacinį kraujo netekimą širdies chirurgijoje ir jo ryšys su krešėjimo sistemos būkle bei genų polimorfizmais]doctoral thesis[2026][R1][M001][139]; ; ; ; ; ; Perioperative bleeding remains one of the most clinically significant complications in cardiac surgery. Traditional assessment methods rely on visual estimation of chest tube drainage, transfusion requirements, or the need for surgical re-exploration; however, these do not accurately reflect actual blood loss and may under- or overestimate bleeding severity. This dissertation develops and validates a novel Hb/kg Index, defined as haemoglobin mass loss per kilogram of patient weight, as an objective and physiologically grounded method for quantifying blood loss in cardiac surgery. The study evaluates associations between the Hb/kg Index and clinical, laboratory, viscoelastic, platelet function, fibrinolytic, and genetic parameters. Machine learning-based clustering was used to identify clinically meaningful blood loss severity groups: Mild, Moderate, and Severe. The study also analyses perioperative dynamics of standard coagulation tests, platelet aggregometry, ROTEM parameters, plasma PAI-1 concentration, and selected single nucleotide polymorphisms: ITGB3 rs5918, FGB rs1800790, and SERPINE1 rs2227631. The results show that the Hb/kg Index provides a robust quantitative framework for blood loss assessment, while viscoelastic testing, particularly FIBTEM A10, has the highest diagnostic value for detecting haemostatic impairment. These findings may contribute to more precise bleeding stratification and individualized haemostatic management in cardiac surgery.
35 48 Item type:Publication, research article[2026][S1][M001][13]; ; ; ; ; ; ; Background: COVID-19 is associated with immune dysregulation and an increased risk of thromboembolic complications, including pulmonary embolism (PE). Identification of dynamic immunological predictors of adverse outcomes remains clinically relevant. This study evaluated associations between coagulation, inflammatory, immunological markers, and in-hospital mortality in patients with severe COVID-19. Material/Methods: In this prospective observational study, 47 hospitalized adults with severe COVID-19 and suspected PE were enrolled. Serum cytokines, coagulation parameters, and cardiac injury biomarkers were assessed at enrollment and on hospital day 5. PE was confirmed using computed tomography pulmonary angiography. Univariable and multivariable binary logistic regression was used to identify predictors of in-hospital all-cause mortality. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC), with internal validation by bootstrap resampling. Results: PE was diagnosed in 19 patients (40.4%), and 13 patients (27.7%) died during hospitalization. Higher standardized day-5 interleukin (IL)-9 and IL-15 levels were associated with mortality in univariable analyses, but neither remained significant after Benjamini-Hochberg false discovery rate correction across the panel of 15 cytokines measured on day 5 (IL-9, q=0.180; IL-15, q=0.210). In an age-adjusted model, day-5 IL-9 remained associated with mortality (adjusted odds ratio per 1-SD increase, 3.331; 95% CI, 1.289-8.608; P=0.013). Apparent discrimination was moderate (AUC 0.774; 95% CI, 0.563-0.984; P = 0.011), but bootstrap validation showed marked coefficient instability. Conclusions: Day-5 IL-9 levels may reflect an evolving risk in severe COVID-19, but the association was sensitive to multiple-testing correction and model instability. This study’s findings are exploratory and require confirmation in larger, externally validated cohorts.
36 21 Item type:Publication, research article[2026][S1][M001,N010][10]; ; ; ; ; ; ; ; ; ; ; ; ; ; ; Best Practice & Research Clinical Gastroenterology, 2026-07-27, vol. 83, p. 1-10The gastrointestinal microbiome has emerged as a critical interface between environmental exposures and host biology, shaping carcinogenesis, tumor behavior, and therapeutic responsiveness across digestive tract malignancies. This narrative review synthesizes current evidence on microbiome testing in esophageal, gastric, colorectal, hepatobiliary, pancreatic, and gastrointestinal stromal cancers, highlighting microbial signatures, emerging translational applications, and the methodological challenges that currently limit clinical implementation. Tumor-specific microbial alterations are considered alongside the broader functional consequences of dysbiosis, including its roles in genotoxicity, immune modulation, and metabolic reprogramming. Particular attention is given to the influence of the microbiome on systemic therapies, especially immune checkpoint inhibition, where microbial diversity, compositional signatures, and antibiotic exposure have been associated with differences in treatment efficacy. Emerging mechanistic insights are highlighted, including the role of microbiota-derived metabolites as key mediators of host-tumor immune interactions. The review further discusses microbiome-directed interventions, including fecal microbiota transplantation and dietary modulation, while critically evaluating the barriers to their clinical translation. Although microbiome profiling has considerable potential to improve risk stratification and therapeutic personalization, current evidence remains largely associative or based on early-phase clinical studies, and no microbiome-based testing strategy has yet been validated for routine clinical use beyond Helicobacter pylori eradication for gastric cancer prevention. Large prospective studies, standardized methodologies, and interventional clinical trials are required before microbiome testing can be integrated into routine precision oncology.
28 - preprint[2026][S1][M001,N010][6]
; ; ; Blood Transfusion, 2026-07-15, vol. 00, no. 00, p. 1-6Human platelet antigens (HPAs) are polymorphic structures on platelet membrane glycoproteins that may induce alloimmune responses after transfusion or pregnancy. Knowledge of HPA distribution in different populations is essential for improving transfusion practice and managing platelet transfusion refractoriness.
23 40 Item type:Publication, research article[2026][S1][M001][14]; ; ; ; ; ; Medicina, 2026-07-06, vol. 62, no. 7, p. 1-14Background and objectives: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with endothelial glycocalyx injury and perioperative endothelial dysfunction. Syndecan-1 is commonly used as a biomarker of glycocalyx shedding, but data on its perioperative changes and their relationship with operative and patient-related factors remain limited. The aim of this study was to evaluate perioperative Syndecan-1 dynamics during coronary artery bypass grafting (CABG) with CPB and to assess associations with ischemia–reperfusion exposure and patient characteristics. Materials and methods: This prospective observational study included 147 patients undergoing elective CABG with CPB. Syndecan-1 concentrations were measured at five time points: before induction of anaesthesia, immediately after aortic cross-clamp application, immediately after aortic declamping, on arrival at the ICU and 24 h after surgery. Perioperative changes were analysed using non-parametric tests, Spearman’s rank correlation analysis and mixed-effects modelling. The study was registered at ClinicalTrials.gov (NCT03491163; registered on 29 March 2018). Results: Syndecan-1 concentrations changed significantly over time (p < 0.001), increasing from a baseline median of 49.74 ng/mL to a peak of 147.78 ng/mL at ICU admission, followed by a partial decline to 65.26 ng/mL at 24 h. Aortic cross-clamp duration was weakly but significantly associated with Syndecan-1 concentration at ICU admission (rs = 0.243, p = 0.003) and with perioperative increases from baseline to ICU admission (ΔS4-1: rs = 0.196, p = 0.017) and from aortic clamping to ICU admission (ΔS4-2: rs = 0.207, p = 0.012). No significant associations were observed between CPB duration and Syndecan-1 concentrations in univariable analyses. In the mixed-effects model, a significant non-linear temporal pattern of Syndecan-1 concentrations was observed (both linear and quadratic time terms, p < 0.001). Male sex (β = 0.247, p = 0.009) and aortic cross-clamp duration (β = 0.016, p = 0.005) were independently associated with higher Syndecan-1 concentrations, whereas smoking status, age, BMI, diabetes status, EuroSCORE II, and CPB duration were not independently associated. Conclusions: Syndecan-1 concentrations increase significantly during cardiac surgery with cardiopulmonary bypass, peaking at ICU admission and partially declining within 24 h. Aortic cross-clamping duration, but not total CPB duration, showed weak associations with glycocalyx shedding. Male sex was independently associated with higher Syndecan-1 concentrations. These findings support ischemia–reperfusion injury as an important contributor to endothelial glycocalyx shedding during cardiac surgery.
24 38 Item type:Publication, research article[2026][S1][M001][26]; ; ; ; ; ; ; ; ; ; ; ; ; International Journal of Molecular Sciences, 2026-07-03, vol. 27, no. 13, p. 1-26The formation of extracellular traps (ETs) through ETosis has emerged as a key mechanism in immunothrombosis. However, the temporal dynamics and clinical significance of ETosis in coronary thrombi of ST-elevation myocardial infarction (STEMI) patients remain incompletely understood. We investigated whether ETosis burden increases with thrombus age and is associated with DNASE1 and TREX1 genetic variants as well as impaired myocardial reperfusion. Thrombus aspirates from 81 STEMI patients undergoing primary percutaneous coronary intervention were histologically classified as fresh (n = 41) or lytic (n = 40). ETosis was quantified by citrullinated histone H3 (CitH3) immunohistochemistry and digital image analysis, complemented by multiplex staining for myeloperoxidase (MPO), CD68, caspase 3, and CD61. Plasma ET-related markers and genotyping of DNASE1 (rs1053874) and TREX1 (rs11797) were also performed. CitH3-positive cells were present in all thrombi but were more abundant in lytic (older) thrombi compared with fresh thrombi (1348 vs. 591 cells/mm2, p < 0.001). Increased ETosis was associated with neutrophil and macrophage infiltration, apoptosis, prolonged ischemia time, elevated systemic inflammation (neutrophil–lymphocyte ratio and C-reactive protein), and impaired myocardial reperfusion (lower TIMI flow grades). Moreover, the DNASE1 GG genotype was associated with higher densities of MPO- and CD68-positive cells, whereas the TREX1 CC genotype was associated with increased densities of CitH3-, MPO-, and CD68-positive cells. This study demonstrates that ETosis increases with coronary thrombus maturation and is associated with local inflammation and impaired reperfusion in STEMI. Genetic variants in DNASE1 and TREX1 may modulate inflammatory cell accumulation within thrombi. These findings suggest ETosis as a potential therapeutic target, particularly in patients with delayed presentation.
20 60 Item type:Publication, [The role of genetic and molecular prognostic markers in the biological activity, invasiveness, recurrence and size of pituitary adenomas]doctoral thesis[2026][R1][N010][148]; ; ; ; ; Hipofizės adenomos (HA) yra viena dažniausių pirminių smegenų navikų formų, kurioms būdingas heterogeniškas biologinis elgesys – nuo kliniškai indolentinių iki invazyvių ir linkusių kartotis navikų. Nepaisant pažangos diagnostikoje ir gydyme, išlieka poreikis identifikuoti patikimus molekulinius prognozinius žymenis, leidžiančius tiksliau prognozuoti ligos eigą ir individualizuoti pacientų priežiūrą. Šio darbo tikslas – įvertinti telomerų biologijos, JAK–STAT bei somatostatino signalinių kelių genetinių variantų, jų koduojamų baltymų ir santykinio leukocitų telomerų ilgio sąsajas su hipofizės adenomos pasireiškimu bei naviko biologiniu elgesiu (aktyvumu, invazyvumu, atkryčiu ir dydžiu). Tyrime kompleksiškai analizuoti telomerų homeostazėje dalyvaujantys genai (TERT, TERC, TEP1, TERF1, TERF2, TNKS2, CTC1, ZNF676), imuninės signalizacijos komponentai (STAT4) bei somatostatino receptorių sistema (SSTR2, SSTR5, AIP). Taip pat vertintas santykinis leukocitų telomerų ilgis ir Ki-67 proliferacijos indeksas. Nustatyta, kad TERC rs35073794 genetinis variantas yra reikšmingai susijęs su hipofizės adenomos pasireiškimu ir jos dydžiu. HA pacientų grupėje nustatytas didesnis santykinis leukocitų telomerų ilgis, o atskiri telomerų reguliacijoje dalyvaujančių genų variantai (pvz., TERF1, TNKS2, CTC1) siejasi su santykiniu leukocitų telomerų ilgiu bei ligos pasireiškimo galimybe. Imuninės signalizacijos analizė parodė, kad STAT4 genetiniai variantai ir padidėjusi šio baltymo koncentracija yra susiję su didesne HA pasireiškimo galimybe. Ki-67 proliferacijos indeksas daugumai tiriamųjų buvo mažas, o statistiškai reikšmingų sąsajų su naviko biologinėmis savybėmis ar tirtais genetiniais variantais nenustatyta. Atliktas tyrimas yra pirmasis Lietuvoje, kuriame kompleksiškai įvertintos telomerų biologijos, imuninės signalizacijos ir somatostatino receptorių sistemos genetinės bei molekulinės sąsajos su hipofizės adenoma. Gauti rezultatai papildo esamas žinias apie HA patogenezę ir sudaro prielaidas tolesniems tyrimams, orientuotiems į prognozinių žymenų paiešką bei individualizuotos pacientų priežiūros tobulinimą.
41 22 Item type:Publication, book[2026][K2d][M001][219]; ; ; ; ; ; ; ; ; Kaunas : Lietuvos pulmonologų ir alergologų draugija, 2026-04-23ĮVADAS. Cistinė fibrozė (CF) - tai genetinė liga, kurią sukelia cistinės fibrozės transmembraninio laidumo reguliatoriaus (angl. cysticfibrosis transmembrane conductance regulator, CFTR) baltymo funkcijos sutrikimas. Šis sutrikimas lemia įvairių egzokrininių liaukų sekrecijos pokyčius, sukelia lėtinį kvėpavimo takų uždegimą, pasikartojančias infekcijas, virškinimo sistemos, kepenų ir kitų organų pažeidimus. Ilgus metus CF laikyta tik vaikų liga, nes sergantieji nesulaukdavo suaugusiųjų amžiaus. Pastaraisiais metais daugėja suaugusių CF sergančių asmenų, o tai siejama tiek su geresne ligos diagnostika, tiek su pažangesne ligos priežiūra. Manoma, kad išgyvenamumas ir toliau ilgės dėl gerėjančių gydymo galimybių, ypač į klinikinę praktiką įdiegus CFTR moduliatorius. Dėl pažangos diagnostikoje, įskaitant visuotinę naujagimių patikrą ir molekulinės genetikos tyrimus, CF galima nustatyti ankstyvame amžiuje, dar iki klinikinių simptomų pasireiškimo. Tai leidžia pradėti intervencijas ir gydymą kuo anksčiau, taip sumažinant komplikacijų riziką ir pagerinant gyvenimo kokybę. Šių nacionalinių rekomendacijų paskirtis - apibrėžti CF diagnostikos algoritmus, tinkamiausius gydymo metodus, pritaikytus mūsų šalies sveikatos priežiūros sistemai, infekcijų kontrolės, komplikacijų prevencijos ir pacientų ilgalaikės stebėsenos standartus. Rengiant rekomendacijas remtasi naujausiomis Europos cistinės fibrozės draugijos (angl. European Cystic Fibrosis Society, ECFS), Jungtinių Amerikos Valstijų (JAV) Cistinės fibrozės fondo (angl. Cystic Fibrosis Foundation, CFF), Jungtinės Karalystės Cistinės fibrozės paramos fondo (angl. Cystic Fibrosis Trust) gairėmis, nacionalinės bei tarptautinės praktikos duomenimis, taip pat epidemiologine situacija mūsų šalyje.
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