Žebrauskaitė-Keblikienė, Gabrielė

Introduction: Severe manifestations of COVID-19 are frequently characterized by acute systemic inflammation, endothelial dysfunction, and a heightened predisposition toward cardiovascular and thrombotic events (1). Many patients who developed severe COVID-19 have pre-existing chronic conditions, such as cardiovascular or metabolic disorders, which are commonly associated with impaired or dysregulated immune response. SARS-CoV-2-induced hypoxia, cytokine-driven inflammation, and direct injury to epithelial and endothelial tissues can disrupt vital biological barriers, such as the intestinal epithelium and the alveolar-capillary junction, thereby facilitating the movement of microbial components into the bloodstream (1-3). The presence of bacterial components may further augment immune activation and inflammatory cascades. Emerging data suggest that bacterial DNA fragments in the bloodstream may trigger inflammatory pathways leading to vascular injury and endothelial activation (4,5). This interaction among viral infection, bacterial translocation, and impaired host immunity may underlie increased susceptibility to complications. Nevertheless, the occurrence, composition, and taxonomic diversity of circulating bacterial DNA in complicated COVID- 19 patients have not been thoroughly characterized. Aim: To use next-generation sequencing (NGS) to detect circulating bacterial DNA and characterize its taxonomic diversity and inter-individual heterogeneity in patients recovering from severe SARS-CoV-2 infection. Methods: The study was conducted at the Laboratory of Molecular Cardiology, Institute of Cardiology, Lithuanian University of Health Sciences. Venous blood samples were obtained after completion of inpatient treatment in patients with a prior episode of severe COVID-19, following acute hospitalization (n=101). Bacterial DNA was amplified by PCR targeting the 16S rRNA gene. Samples yielding detectable 16S rRNA products underwent sequencing using Oxford Nanopore Technologies (ONT, The Oxford Science Park, UK). Taxonomic classification of both 16S rRNA amplicon data and shotgun metagenomic reads was performed using the EPI2ME platform (ONT). Reads were classified at the class level. Patients from the same clinical cohort in whom bacterial DNA was not detected served as an internal comparator group. Additionally, clinical and laboratory parameters related to cardiac injury, systemic inflammation, and coagulation were assessed to provide a clinical context. Results: Circulating bacterial DNA was detected in most of the patients (76% of the total cohort, n=101). The analysis highlighted significant variation among individual microbial profiles. Taxonomic profiling demonstrated that Gammaproteobacteria and Alphaproteobacteria were the most dominant taxa, occurring in 95% of the bacterial DNA- positive samples. In comparison, Betaproteobacteria were identified in 43% of cases, while Bacilli and Actinomycetes were less frequent, appearing in 33% and 29% of the analyzed samples, respectively. Conclusions: Bacterial DNA is detectable in the blood of patients recovering from severe COVID-19 and exhibits marked interindividual diversity. The recurrent detection of Gammaproteobacteria may indicate a non-random microbial pattern; however, further studies with rigorous contamination controls are required. These results underscore the need for further research into how bacterial components might exacerbate systemic inflammation in viral infections.

Introduction Infective endocarditis (IE) remains associated with high morbidity and mortality despite advances in diagnosis and treatment [1,2]. In recent years, increasing attention has been paid to atypical presentations of IE, particularly cases presenting with neurological symptoms and embolic events, which complicate early diagnosis and occur in approximately 20–55% of patients [1,3]. Case Presentation A 47-year-old male was hospitalized after a generalized seizure. Neurological examination revealed no focal deficits. Initial brain CT showed no acute pathology, and inflammatory markers were normal. During hospitalization, the patient developed fever, elevated inflammatory markers, haemorrhagic skin rash, and superficial thrombophlebitis. Brain MRI revealed multiple lacunar infarctions in the left middle cerebral artery territory, consistent with embolic events. Blood cultures grew Staphylococcus aureus, raising suspicion of infective endocarditis. TEE demonstrated a large aortic valve vegetation (~16 mm) with cusp perforation and severe regurgitation. The patient later disclosed intravenous drug use with injections into the feet. Due to severe aortic regurgitation, large vegetation size, and worsening hemodynamic status, a guideline-based indication for surgery was established, and successful aortic valve replacement with a mechanical prosthesis was performed. This case is notable for its atypical initial presentation with seizure and normal inflammatory markers. Discussion This case report is consistent with the latest European Society of Cardiology guidelines, which indicate that infective endocarditis may initially present with neurological manifestations and embolic events, leading to diagnostic delay [1]. Although intravenous drug use is most commonly associated with right-sided endocarditis, Staphylococcus aureus also can involve left-sided heart valves, causing rapid valvular destruction and severe embolic complications [1,2]. Neurological embolic events remains an unfavourable complication of leftsided infective endocarditis [1,3]. Conclusions Infective endocarditis can present with neurological symptoms and embolic events even in the absence of typical infectious signs. Early recognition and timely echocardiography are essential to reduce diagnostic delay and adverse outcomes.

Introduction Heart transplantation is the definitive treatment for selected patients with advanced heart failure (HF) [1]. This case highlights the challenges of managing heart transplant candidates when eligibility is lost due to newly diagnosed, life-threatening non-cardiac conditions. Case Presentation A 60-year-old male with non-ischemic dilated cardiomyopathy progressed to advanced HF (NYHA IV) despite optimal guideline-directed medical and device-based therapy, with severely reduced left ventricular ejection fraction (20%) and marked left ventricular dilatation. Following a comprehensive multidisciplinary assessment, he was listed for heart transplantation in late 2024. During follow-up, a duodenal tumor was diagnosed and confirmed by biopsy. Emergency surgery was required due to duodenal perforation and peritonitis. Histology revealed a well-differentiated duodenal neuroendocrine tumor (NET G1, ≥pT1) with positive resection margins (R1). The postoperative course was complicated by abdominal sepsis, septic shock, and multiple organ dysfunction syndrome (MODS). Following this, the patient developed severe HF decompensation with recurrent hypotension (70/40 mmHg), limiting further medical therapy. Due to active malignancy with uncertain oncological radicality and recent severe sepsis, the patient was no longer eligible for heart transplantation. Discussion Heart transplantation eligibility requires continuous reassessment in patients with advanced HF [2]. Active malignancy and recent severe infection are recognized contraindications due to increased perioperative risk and cancer recurrence under immunosuppression [1]. When transplantation is no longer feasible, management relies on guideline-directed medical therapy; however, treatment options may be limited due to hypotension or other comorbidities. In such scenarios, management shifts from algorithmbased treatment to individualized, multidisciplinary decision-making, highlighting limited therapeutic options in advanced HF care [2–4]. Conclusions This case demonstrates how a newly diagnosed malignancy and severe infectious complications may rapidly eliminate heart transplantation as a treatment option, even in previously eligible candidates. In advanced HF, such situations may result in a therapeutic dead end with limited alternative options.

Introduction Severe forms of COVID-19 are linked to significant systemic inflammation, endothelial dysfunction, and an elevated risk of thrombotic and cardiovascular complications (1). SARSCoV-2-induced hypoxia, cytokine-driven inflammation, and direct injury to epithelial and endothelial tissues can disrupt vital biological barriers facilitating the movement of microbial components into the bloodstream (1–3). Increasing evidence indicates that microbial components in the bloodstream may contribute to inflammation-related endothelial activation and vascular damage (4,5). This interaction among viral infection, bacterial translocation, and impaired host immunity may underlie increased susceptibility to complications. Nevertheless, the occurrence, composition, and taxonomic diversity of circulating bacterial DNA in complicated COVID-19 patients have not been thoroughly characterized. Aim To investigate the presence, taxonomic diversity, and variability of circulating bacterial DNA in the venous blood of patients hospitalized with severe COVID-19 infection, using nextgeneration sequencing. Methods The study was conducted at the Laboratory of Molecular Cardiology of the Institute of Cardiology at the Lithuanian University of Health Sciences. Venous blood samples were collected from 65 patients after hospitalization for severe COVID-19 infection. PCR targeting the 16S rRNA gene was employed to amplify bacterial DNA from patient samples. At the time of analysis, sequencing was completed for 21 samples, while analysis of the remaining samples is ongoing. Subsequently, microbiome profiling using Oxford Nanopore Technologies (ONT) sequencing was performed only on samples containing 16S rRNA gene sequences. Taxonomic interpretation was performed at the class level. A healthy control group was not included, as previous studies conducted in the same laboratory have not demonstrated the presence of circulating bacterial DNA in healthy individuals. Clinical and laboratory parameters related to cardiac injury, inflammation and coagulation were evaluated. Results Bacterial 16S rRNA gene sequences were detected in 20 out of 21 analyzed samples (95.2%). Gammaproteobacteria and Alphaproteobacteria were the predominant classes, detected in 95.2% of samples. Betaproteobacteria were identified in 42.9% of samples, while Actinomycetes and Bacilli were present in 28.6% and 33.3% of cases, respectively. Within one year after hospitalization, 14 of the 21 patients were diagnosed with cardiovascular conditions. Conclusions Circulating bacterial DNA is detectable in the blood of patients after hospitalization for severe COVID-19 infection, and its interpatient variability is evident. The relevance of the Gammaproteobacteria class indicates a non-random microbial DNA signal and supports further investigation into the potential role of bacterial components in systemic inflammation.

On 11 March 2020, the outbreak of COVID-19 was declared a pandemic and became one of the main contributors to global mortality. Despite the end of the COVID-19 pandemic, the coronavirus 2019 disease remains a significant public health issue. The novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a respiratory virus associated with a high risk of thrombotic complications. Thrombotic events are linked to increasing disease severity and mortality rates. The article reviews the current knowledge of thrombosis following COVID-19 infection to elucidate the pathogenesis, diagnostics, possible treatment options, and associated prophylaxis. Objective: to review the latest scientific publications about COVID-19-related thrombosis. Methods: literature sources were searched in the following databases: PubMed, Up ToDate, and Cochrane. The newest articles on the topic were evaluated and analyzed. Conclusions: Although the exact pathophysiology of COVID-19-related thrombosis remains unclear, several factors are known to contribute to its development. These include acute inflammatory reactions, increased levels of coagulation factors, platelet and endothelial activation, and the formation of extracellular neutrophil traps. Scoring systems and elevated D-dimer levels are valuable for identifying patients at risk. Despite certain limitations, Doppler ultrasound and CTPA (computed tomography pulmonary angiography) remain key diagnostic tools. Comprehensive care involves primary prophylaxis with anticoagulants and mechanical therapies, as well as secondary prevention through early detection and prompt treatment of thrombotic events. This multifaceted approach is essential to improving outcomes for patients with COVID-19 and mitigating the impact of thrombotic complications.

Daugumai pacientų, persirgusių COVID-19, simptomai visiškai išnyksta, tačiau beveik 65 mln. žmonių visame pasaulyje gali pasireikšti lėtinė COVID-19 liga („ilgasis COVID sindromas"). Viena dažniausių jos klinikinių išraiškų - širdies ir kraujagyslių sistemos ligų komplikacijos. Lėtinė COVID-19 liga gali paveikti įvairias organizmo sistemas, sukelti naujų simptomų, lėtinių ligų bei komplikacijų, kurios neigiamai veikia gyvenimo kokybę ir kelia didelius iššūkius sveikatos priežiūros sistemai. Siekiant kurti veiksmingas gydymo strategijas, nagrinėjamas ryšys tarp lėtinės COVID-19 ligos ir širdies ir kraujagyslių sistemos pažeidimo. Šioje apžvalgoje aptariami dažniausi simptomai, galimos komplikacijos, rizikos veiksniai ir mechanizmai, lemiantys širdies ir kraujagyslių sistemos pažeidimus sergantiesiems lėtine COVID-19 liga.

The benefits of intravascular imaging-guided percutaneous coronary interventions (PCI) are well established. Intravascular imaging guidance improves short- and long-term outcomes, especially in complex PCI. Optical coherence tomography (OCT) has a higher resolution than intravascular ultrasound. However, the usage of OCT is mainly limited by the need to use contrast for flushing injections, which increases the risk of contrast-induced acute kidney injury, especially in patients with underlying chronic kidney disease. The aim of this study was to prove that flushing techniques with normal saline instead of contrast can be used in OCT imaging and can generate high-quality images.

Background: Familial hypercholesterolemia (FH) is an inherited disorder with a prevalence 1:250. FH is caused by variants in the genes coding low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) [1,2]. It is crucial to identify patients with suspected FH and start treatment to prevent coronary artery disease (CAD). Aim: To compare FH patients antilipidemic treatment peculiarities. Methods: This is a retrospective cohort study of patients with a suspected FH. Subjects were included in the study according to the criteria of the Dutch Lipid Clinic (DLC), divided into three groups 1. patients with APOB variant; 2. patients with the LDLR variant. 3. patients without previously described variants. Next generation sequencing was used to sequence the coding regions. Statistical analysis was performed using SPSS 29.0.1. Results: A total of 45 patients were enrolled - 27 (60%) men and 18 (40%) women, mean age

• 47.93 years (SD=9.391). After genetic sequencing, 5 (11%) patients were diagnosed with APOB rs5742904, 2 (4%) patients had an LDLR rs879254754 variant. 35 (77%) subjects were using antilipidemic drugs (Chart 1). Most prescribed medications- high intensity dosage atorvastatin. 5 APOB rs5742904 variant patients vs. 1 LDLR rs879254754 variant patient were using antilipidemic drugs with a men LDL Cholesterol (LDL-C) 5,894 (SD=0,805) vs. 6,6 (SD=0,651) mmol/l. Patients with positive FH variant, had lower triglycerides (TGC) rate (1,82 vs. 3,26 mmol/l, p<0,02). Conclusion: According to our study, only three quarters of patients are treated based on recent European Society of Cardiology guidelines.

INTRODUCTION Cascade screening and genetic testing have become one of the most effective methods for early detection of familial hypercholesterolemia (FH) identification and early prevention of coronary artery disease (CAD) [1]. FH is usually caused by variants in the genes coding for the low-density lipoprotein receptor (LDLR). Variants in the genes for apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) have also been associated with FH [2]. The results of our pilot study showed that APOB was widespread in our population.

PURPOSE To estimate the prevalence of APOB variants in FH patient’s cohort.

METHODS This is a retrospective cohort study of patients with a suspected diagnosis of FH who were treated at a tertiary center between February 2022 and June 2023. Patients were included in the study according to the criteria of the Dutch Lipid Clinic (DLC). Patients were divided into three groups according to the results of the genetic tests: 1. patients with APOB variant; 2. patients without previously described variants causing FH; 3. patients with the LDLR variant. Next generation sequencing was used to sequence the coding regions. Statistical analysis was performed using SPSS 29.0.1. statistical software.

RESULTS A total of 45 patients were enrolled in this study, including 27 (60%) men and 18 (40%) women, with a mean age of 47.93 years (SD=9.391). After genetic sequencing evaluation, 7 (16%) patients were diagnosed with APOB rs5742904 variant causing FH. In addition, 2 (4%) patients were found to have an LDLR rs879254754 variant. As the patients with an LDLR variant had no CHD symptoms, no further screening was performed.

No statistically significant demographic and clinical differences were found between the groups. The distribution of DLC network scores is shown in Figure 1. The only significant difference between the groups was found in the patients with the APOB rs5742904 variant, where more patients had the highest DLC score.

The most frequently affected segments in both groups were: S1, S6 and S7. Conversely, the least affected segments were: S10, S14, S15 (Figure 2). A remarkable result was seen in the S2 segment, where complete occlusion occurred significantly more frequently in patients with an APOB rs5742904 variant than in patients without this variant.

CONCLUSION Contrary to what is mentioned in the literature, there were more people with APOB rs5742904 mutation than with LDLR in our study. We also found that patients with the APOB rs5742904 mutation had statistically significantly more occlusions in the right coronary artery.

76 metų moteris 2023 m. rugpjūčio 18–25 d. gydyta LSMU Kauno ligoninės Vidaus ligų skyriuje dėl E. coli sukelto ūminio pielonefrito, skirtas antibakterinis gydymas cefuroksimu, sumažėjus uždegiminiams rodikliams išleista toliau gydytis ambulatoriškai. 2023-09-11 atsirado febrilus karščiavimas iki 39,0 °C, progresavo bendras silpnumas, atsirado apetito stoka, 2023-09-14 pacientė kreipėsi į šeimos gydytoją, atlikus bendrą šlapimo tyrimą (BŠT) diagnozuota leukociturija, būklė vertinta kaip šlapimo takų infekcija, skirtas antibakterinis gydymas cefuroksimu po 500 mg x 2 peroraliai (p/os).