Recurrent Infective Endocarditis of the Mitral Valve after Orthotopic Heart Transplantation.

Introduction: Orthotopic heart transplantation is the gold standard for the treatment of advanced heart failure in the absence of contraindications. Infective endocarditis is a rare complication in patients after heart transplantation. The treatment of endocarditis after heart transplantation is challenging since there is a need for ongoing immunosuppression. Case description: We present the case of a 51-year-old orthotopic heart transplant recipient enrolled in a chronic dialysis program, in whom we diagnosed and successfully treated recurrent infective endocarditis of the mitral valve caused by Enterococcus and Enterobacter species. Despite the complicated course of the disease, the treatment was successful. Conclusions: Recurrent infective endocarditis after heart transplantation can be treated successfully with a multidisciplinary approach and robust antimicrobial therapy. LEARNING POINTS: There is a high risk of bacteraemia and subsequent endocarditis in patients with recurrent catheter-related sepsis.The spectrum of bacteria causing endocarditis in patients after heart transplantation differs from that in the general population.Scrupulous targeted antibiotic treatment is warranted for the treatment of immunosuppressed patients with endocarditis.

A Fast-Growing Myxoma of the Left Atrium.

Introduction: Myxoma of the left atrium is a less typical cause of mitral obstruction. If this develops, a flash pulmonary oedema can be the first manifestation. Case description: We present a case report of a 50-year-old woman who was admitted to our internal department because of dyspnoea. The patient overcame a stroke three years before the index hospitalisation with a negative transthoracic echocardiography. By anamnesis and physical examination, an exacerbation of COPD was assumed, and the patient was treated accordingly. As the patient showed numerous risk factors for heart failure with preserved ejection fraction, transthoracic echocardiography was performed. A large polypoid mass was found in the left atrium, which caused severe mitral obstruction. Subsequent transoesophageal echocardiography confirmed this finding. The patient underwent urgent cardiac surgery, and the tumour was successfully resected. A histological examination revealed a cardiac myxoma. After the cardiac surgery the patient felt well, and no recurrence of the tumour occurred. Conclusions: We provide a case report of a fast-growing myxoma that was incidentally found in a patient with dyspnoea. We highlight the fast growth rate of the tumour and the potential for misdiagnosed signs of pulmonary oedema caused by mitral obstruction. LEARNING POINTS: Myxomas are the most common primary tumours of the heart, which can manifest a variety of symptoms such as fever, weight loss, thromboembolism, or mitral obstruction.The symptoms of acute exacerbation of COPD and cardiogenic pulmonary oedema can overlap and can be difficult to differentiate by anamnesis and physical examination alone.Transthoracic echocardiography has a high sensitivity for cardiac masses and is the examination of choice when these are suspected.

A Rare Early-Onset Fatal Complication after Transarterial Chemoembolization: A Case Report and Review of the Literature.

Transarterial chemoembolization (TACE) is a minimally invasive treatment for liver cancer, often employed as a bridging therapy or destination treatment for non-operable cases. This case report discusses an 82-year-old woman with a large hepatocellular carcinoma (HCC) who underwent elective TACE due to the high surgical risk associated with her tumor size. Unexpectedly, the patient experienced liver rupture 20 h post-procedure, leading to acute surgical intervention. Despite successful hemostasis during surgery, the patient succumbed to progressive multi-organ failure. We aimed to search the PubMed database for documented cases of ruptured HCC after TACE. This study highlights risk factors for spontaneous HCC rupture and specific factors associated with TACE-induced rupture. Transarterial embolization (TAE) is currently favored as the treatment method for spontaneous ruptures, while the optimal therapy for TACE-induced ruptures remains unclear. In conclusion, this case underscores the importance of recognizing the rare complication of HCC rupture post-TACE and the need for personalized risk assessment. While TAE emerges as a primary treatment choice, the lack of consensus necessitates further studies to establish evidence-based approaches for managing this uncommon yet life-threatening complication.

Application of Liquid Chromatography Coupled to Mass Spectrometry for Direct Estimation of the Total Levels of Adenosine and Its Catabolites in Human Blood.

Adenosine is a multifunctional nucleoside with several roles across various levels in organisms. Beyond its intracellular involvement in cellular metabolism, extracellular adenosine potently influences both physiological and pathological processes. In relation to its blood level, adenosine impacts the cardiovascular system, such as heart beat rate and vasodilation. To exploit the adenosine levels in the blood, we employed the liquid chromatography method coupled with mass spectrometry (LC-MS). Immediately after collection, a blood sample mixed with acetonitrile solution that is either enriched with 13C-labeled adenosine or a newly generated mixture is transferred into the tubes containing the defined amount of 13C-labeled adenosine. The 13C-enriched isotopic adenosine is used as an internal standard, allowing for more accurate quantification of adenosine. This novel protocol for LC-MS-based estimation of adenosine delivers a rapid, highly sensitive, and reproducible means for quantitative estimation of total adenosine in blood. The method also allows for quantification of a few catabolites of adenosine, i.e., inosine, hypoxanthine, and xanthine. Our current setup did not allow for the detection or quantifying of uric acid, which is the final product of adenosine catabolism. This advancement provides an analytical tool that has the potential to enhance our understanding of adenosine's systemic impact and pave the way for further investigations into its intricate regulatory mechanisms.

Unilateral upper and lower limb ischemia mimics stroke: a case report.

BACKGROUND: Although stroke and acute limb ischemia seem easily distinguishable by anamnesis and physical examination, symptoms may overlap and sometimes mislead the examiner. Such a situation can arise in the occurrence of unilateral neurological symptoms affecting the upper and lower limbs at the same time. As timely diagnosis and a correct therapeutic intervention are crucial to prevent irreversible damage in both diseases, knowledge of the possibility of one disease mimicking the other is essential. We present a unique case of acute unilateral upper and lower limb ischemia mimicking an acute stroke. CASE PRESENTATION: A 69-year-old Caucasian patient with known atherosclerotic risk factors was admitted to the emergency department with a suspected stroke with unilateral paresthesia. After a comprehensive examination of the patient with the need for repeated reevaluation and a negative brain computed tomography scan, acute left-sided upper and lower limb ischemia was eventually diagnosed. The patient underwent surgical revascularization of the upper and lower limbs with a satisfactory result and was discharged from the hospital after a few days. CONCLUSION: It is of utmost importance to always stay alert for stroke mimics, as overlooking can lead to severe complications and delay adequate therapy. Our case shows that persistent diagnostic effort leads to successful treatment of the patient even on rare occasions, as is the acute unilateral upper and lower limb ischemia.

Role of Platelets in Rheumatic Chronic Autoimmune Inflammatory Diseases.

Platelets are essential in maintaining blood homeostasis and regulating several inflammatory processes. They constantly interact with immune cells, have immunoregulatory functions, and can affect, through immunologically active substances, endothelium, leukocytes, and other immune response components. In reverse, inflammatory and immune processes can activate platelets, which might be significant in autoimmune disease progression and arising complications. Thus, considering this interplay, targeting platelet activity may represent a new approach to treatment of autoimmune diseases. This review aims to highlight the role of platelets in the pathogenic mechanisms of the most frequent chronic autoimmune inflammatory diseases to identify gaps in current knowledge and to provide potential new targets for medical interventions.

High On-Treatment Platelet Reactivity in Patients Undergoing Complex Percutaneous Coronary Interventions.

Patient response to P2Y12 inhibitor therapy is heterogeneous, and those with high on-treatment platelet reactivity (HTPR) are at an increased risk of thrombotic complications. The aim of our study was to determine whether selecting a high-risk patient group of individuals after complex percutaneous coronary intervention (PCI) would show the clinical benefit of HTPR testing for preventing thrombotic complications. Blood samples of patients after complex PCI were acquired 1 day and 1 month after the intervention. The samples were tested using vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) and platelet function assay (PFA). The occurrence of clinically significant stent thrombosis with repeated revascularization of the target vessel was observed over a 1-year period. One day after PCI, 37% of patients had HTPR as established by VASP-P. One month after PCI, the percentage of patients with HTPR decreased to 30.9%. According to PFA, 1 day after PCI, 33.3% of patients had HTPR. This percentage declined to 19.8% after 1 month. All measurements identified a significantly higher proportion of HTPR in patients on clopidogrel compared to ticagrelor and prasugrel. Two cases of early stent thrombosis and 1 case of late stent thrombosis were identified. Further study of adenosine diphosphate receptor blocker on-treatment response in patients undergoing complex PCI is necessary.

A Functional Assay for the Determination of Heparin-Induced Thrombocytopenia via Flow Cytometry.

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin therapy (both unfractionated heparin and low-molecular-weight heparin). In our study, we examined a group of 122 patients with suspected HIT. The samples of all patients were analyzed in the first step using an immunoassay (ID-PaGIA Heparin/PF4, Hemos1L-Acustar HIT IgG, ZYMUTEST HIA Monostrip IgG) to detect the presence of antibodies against heparin-PF4 complexes (platelet factor 4). When the immunoassay was positive, the sample was subsequently analyzed for HIT with a functional flow cytometry assay, the HITAlert kit, the purpose of which was to demonstrate the ability of the antibodies present to activate platelets. A diagnosis of HIT can be made only after a positive functional test result. In this article, we present an overview of our practical experience with the use of the new functional method of analysis, HIT, with flow cytometry. In this work, we compared the mutual sensitivity of two functional tests, SRA and the flow cytometry HITAlert kit, in patients perceived as being at risk for HIT. This work aims to delineate the principle, procedure, advantages, pitfalls, and possibilities of the application of the functional test HITAlert using flow cytometry.

The Anti-Thrombotic Effects of PCSK9 Inhibitors.

Atherosclerosis is the primary process that underlies cardiovascular disease. The connection between LDL cholesterol and the formation of atherosclerotic plaques is established by solid evidence. PCSK9 inhibitors have proven to be a valuable and practical resource for lowering the LDL cholesterol of many patients in recent years. Their inhibitory effect on atherosclerosis progression seems to be driven not just by lipid metabolism modification but also by LDL-independent mechanisms. We review the effect of PCSK9 inhibitors on various mechanisms involving platelet activation, inflammation, endothelial dysfunction, and the resultant clot formation. The main effectors of PCSK9 activation of platelets are CD36 receptors, lipoprotein(a), oxidised LDL particles, tissue factor, and factor VIII. Many more molecules are under investigation, and this area of research is growing rapidly.

Modelling Duchenne muscular dystrophy in vitro with newly generated, blood cell-derived induced pluripotent stem cell line ORIONi003-A.

Here, we present newly derived in vitro model for modeling Duchenne muscular dystrophy. Our new cell line was derived by reprogramming of peripheral blood mononuclear cells (isolated from blood from pediatric patient) with Sendai virus encoding Yamanaka factors. Derived iPS cells are capable to differentiate in vitro into three germ layers as verified by immunocytochemistry. When differentiated in special medium, our iPSc formed spontaneously beating cardiomyocytes. As cardiomyopathy is the main clinical complication in patients with Duchenne muscular dystrophy, the cell line bearing the dystrophin gene mutation might be of interest to the research community.

How to Treat Today? Oral and Facial Cancer-Associated Venous Thromboembolism.

The exact incidence of cancer-associated venous thromboembolism (CA-VTE) in patients with oral and facial cancer (OFC) is not exactly known, and this risk is empirically considered to be low. However, this suggestion may result in disease underdiagnosis, prolong the initiation of adequate therapy, and consecutively increase CA-VTE-related morbidity and mortality. In addition, there might be specific clinical problems in the treatment of CA-VTE in patients with oral and facial cancer, such as swallowing difficulties, that might limit the possibilities of oral anticoagulation. Finally, there are limited data regarding the optimal treatment of CA-VTE in patients with oral and facial cancer, and this includes data on novel therapeutic strategies, including the use of direct oral anticoagulants. This article reviews current data on the optimal treatment strategy for CA-VTE in patients with OFC.

MiR-126 and miR-146a as markers of type 2 diabetes mellitus: a pilot study.

INTRODUCTION: Despite known risk factors for developing type 2 diabetes mellitus (T2D), the research community still tries to discover new markers that would widen our diagnostic and therapeutic approach to diabetes. Therefore, research on microRNA (miR) in diabetes thrives. This study aimed to assess the utility of miR-126, miR-146a, and miR-375 as novel diagnostic markers for T2D. METHODS: We examined relative quantities of miR-126, miR-146a, and miR-375 in the serum of patients with established type 2 diabetes mellitus (n = 68) and compared these with a control group (n = 29). We also undertook a ROC analysis of significantly changed miR to examine their use as a diagnostic test. RESULTS: MiR-126 (p < 0.0001) and miR-146a (p = 0.0005) showed a statistically significant reduction in patients with type 2 diabetes mellitus. MiR-126 also proved to be an exceptional diagnostic test in our study cohort, with high sensitivity (91 %) and specificity (97 %). We did not find any difference in our study groups' relative quantities of miR-375. CONCLUSION: The study proved a statistically significant reduction of miR-126 and miR-146a in patients with T2D (Tab. 4, Fig. 6, Ref. 51). Text in PDF www.elis.sk Keywords: microRNA, epigenetics, genomics, type 2 diabetes mellitus, miR-126, miR-146a and miR-375.

A high-throughput liquid chromatography-tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma.

Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non-compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one-step extraction procedure in 96-well formate for phospholipid and protein removal was used for sample pre-treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0-1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.

COVID-19 and the Response to Antiplatelet Therapy.

The coronavirus SARS-CoV2 disease (COVID-19) is connected with significant morbidity and mortality (3.4%), disorders in hemostasis, including coagulopathy, activation of platelets, vascular injury, and changes in fibrinolysis, which may be responsible for an increased risk of thromboembolism. Many studies demonstrated relatively high rates of venous and arterial thrombosis related to COVID-19. The incidence of arterial thrombosis in severe/critically ill intensive care unit-admitted COVID-19 patients appears to be around 1%. There are several ways for the activation of platelets and coagulation that may lead to the formation of thrombi, so it is challenging to make a decision about optimal antithrombotic strategy in patients with COVID-19. This article reviews the current knowledge about the role of antiplatelet therapy in patients with COVID-19.

Resistance on the Latest Oral and Intravenous P2Y12 ADP Receptor Blockers in Patients with Acute Coronary Syndromes: Fact or Myth?

Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called "high on-treatment platelet reactivity" or "resistance") could be connected with increased risk of adverse ischemic events, such as myocardial re-infarction, target lesion failure and stent thrombosis. In addition, several risk factors have been proposed as factors associated with the phenomenon of inadequate response on novel ADPRB. These include obesity, multivessel coronary artery disease, high pre-treatment platelet reactivity and impaired metabolic status for prasugrel, as well as elderly, concomitant therapy with beta-blockers, morphine and platelet count for ticagrelor. There is no literature report describing nonoptimal therapeutic response on cangrelor, and cangrelor therapy seems to be a possible approach for overcoming HTPR on prasugrel and ticagrelor. However, the optimal therapeutic management of "resistance" on novel ADPRB is not clear and this issue requires further research. This narrative review article discusses the phenomenon of high on-treatment platelet reactivity on novel ADPRB, its importance in clinical practice and approaches for its therapeutic overcoming.

Tailored Direct Oral Anticoagulation in Patients with Atrial Fibrillation: The Future of Oral Anticoagulation?

Direct oral anticoagulants (DOAC) are currently the drug of choice for drug prevention of stroke or systemic embolism in patients with atrial fibrillation (AF). However, repeated ischemic stroke or systemic embolism and bleeding while on DOAC is still a challenging clinical phenomenon in the management of future long-term anticoagulation. It is not known whether tailoring the DOAC therapy to achieve optimal therapeutic drug levels could improve the clinical course of DOAC therapy. To be able to tailor the therapy, it is necessary to have a valid laboratory method for DOAC level assessment, to be aware of factors influencing DOAC levels and to have clinical options to tailor the treatment. Furthermore, the data regarding clinical efficacy/safety of tailored DOAC regimes are still lacking. This article reviews the current data on tailored direct oral anticoagulation in patients with AF.

DNA Polymorphisms in Pregnant Women with Sticky Platelet Syndrome.

Sticky platelet syndrome (SPS) is a thrombophilia caused by the increased aggregability of platelets in response to the addition of low concentrations of epinephrine (EPI) and/or adenosine diphosphate (ADP). Some of the single nucleotide polymorphisms (SNP), alleles and haplotypes of platelet glycoprotein receptors were proved to have a role in the etiology of thrombotic episodes When comparing SPS and the control group, in VEGFA rs3025039, the p value for both CC vs. TT and CT vs. TT analyses was <0.001. Interestingly, no minor TT genotype was present in the SPS group, suggesting the thrombotic pathogenesis of recurrent spontaneous abortions (RSA) in these patients. Moreover, we found a significant difference in the presence of AT containing a risky A allele and TT genotype of ALPP rs13026692 (p = 0.034) in SPS patients when compared with the controls. Additionally, we detected a decreased frequency of the GG (CC) genotype of FOXP3 rs3761548 in patients with SPS and RSA when compared with the control group (p value for the CC (GG) vs. AA (TT) 0.021). This might indicate an evolutionary protective mechanism of the A (T) allele in the SPS group against thrombotic complications in pregnancy. These results can be used for antithrombotic management in such pregnant patients.

Myocardial free wall rupture as a complication of STEMI.

Myocardial free wall rupture is a rare, but serious complication of acute myocardial infarction with high mortality. We present a case of a 64-year-old patient with this devastating complication of an anterior ST segment elevation myocardial infarction (STEMI) with a prolonged time delay. Cardiac surgery was not performed due to prohibitive surgical risk and predicted poor prognosis. We describe our successful therapeutic intervention consisting of immediate pericardial drainage, vasoactive and inotropic support, intraaortic balloon pump placement and continuous veno-venous hemodialysis. This combined therapy led to patient stabilization and after incremental clinical improvement the patient was able to return to a normal life. After several months a long-term mechanical circulatory support was implanted as a bridge to heart transplant.

SARS-CoV-2 Infection-Associated Aortic Thrombosis Treated with Oral Factor Xa Inhibition.

Coronavirus disease 2019 (COVID-19) is an acute complex systemic disorder caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).While SARS-CoV-2 is known to cause significant pulmonary disease, various extrapulmonary manifestations of COVID-19 have also been reported. Growing evidence suggests that COVID-19 is associated with coagulopathy leading to micro and macrovascular complications. Although in patients with COVID-19, venous thromboembolic events are more frequent, arterial thrombosis also occurs at an increased rate. These often lead to acute life-threatening ischemia, which requires urgent diagnosis and treatment. We present case reports of two patients with an abnormal thrombus formation in the thoracic aorta who recently overcame COVID-19, which led to systemic embolism and splenic infarction. Ambulatory oral factor Xa inhibitor therapy led to aortic thrombosis resolution in both patients.