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.

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.

Gastrointestinal Complications of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome Managed By Parenteral Nutrition.

MELAS - an acronym for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes - is a multiorgan disease caused by a mutation in mitochondrial DNA (mtDNA). Its clinical manifestations are highly variable; mainly stroke-like episodes, seizures, recurrent headaches, or muscle weakness. However, gastrointestinal complications such as chronic intestinal pseudo-obstruction (IPO), pancreatitis, gastroparesis and hepatopathy are also common. In this report we describe a young patient with gastrointestinal complication of MELAS which led to superior mesenteric artery syndrome (SMAS). It is rare but not surprising combination and should be considered in cases with significant weight loss and resistance to symptomatic treatment. The optimal energy support is the main pillar of the treatment. LEARNING POINTS: Gastrointestinal complications of MELAS such as chronic intestinal pseudo-obstruction, pancreatitis and gastroparesis can lead to undernutrition.Superior mesenteric artery syndrome is a rare condition but should be considered in cases with significant weight loss and resistance to symptomatic treatment.Optimal caloric intake and energy support can improve the condition of patients with MELAS.

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.

Urinary tract infection in the context of mini-invasive procedures after kidney transplantation.

INTRODUCTION: The use of antibiotic prophylaxis in invasive procedures is generally accepted and highly recommended. The question is the need to apply antibiotic prophylaxis even in the case of mini-invasive procedures in the post-transplantation period. The aim of the study was to dermine the occurrence of infectious complications during mini-invasive procedures (pig-tail extraction, protocol biopsy) withou the use of antibiotic (ATB) prophylaxis. The secondary aim was to identify risk factors for a positive urine culture finding at the time of mini-invasive procedures. MATERIAL: This is a prospective monocentric study in which pacients after kidney transplantation at Transplantation centrum in Martin were included (n = 68). We investigated the incidence of positive urine findings at the time of pig-tail extraction (6 weeks after transplantation) and at the time of protocol biopsy (3 months after transplantation) with comparison within the group with and without ATB prophylaxis. RESULTS: Patients in group without ATB prophylaxis had a significantly higher tacrolimus value at the time of pig-tail extraction (p = 0.0274) and a significantly higher dose of mycophenolic acid at the time of protocol biopsy (p = 0.0429). We did not confirm significant difference in occcurence of positive urine findings at the time of pig-tail extraction or at the time of protocol biopsy. We completed a univariate logistic regression in order to identify a potential risk predictor for positive urine findings at the time of pig-tail extraction and protocol biopsy. None of the monitored parameters, including ATB prophylaxis, was confirmed as risk or protective factor. CONCLUSION: The use of antibiotic prophylaxis during mini-invasive procedures (pig-tail extraction, protocol biopsy) in the posttransplantation period had no effect on positive culture findings at our department. Based on our analysis, we therefore do not use antibiotic prophylaxis in the case of these procedures at our centre (Tab. 3, Fig. 6, Ref. 23).

Age, body composition parameters and glycaemic control contribute to trabecular bone score deterioration in acromegaly more than disease activity.

Introduction: Impairment of bone structure in patients with acromegaly (AP) varies independently of bone mineral density (BMD). Body composition parameters, which are altered in patients with acromegaly, are important determinants of bone strength. Purpose: The aim of this study was to examine BMD and lumbar trabecular bone score (TBS) by dual-energy X-ray absorptiometry (DXA) and to assess its relationship with disease activity, age, glucose metabolism, and body composition parameters. Methods: This cross-sectional prospective study involved 115 patients with acromegaly (70 F, 45 M) and 78 healthy controls (CON) (53 F, 25 M) matched for age, gender, and BMI. Bone mineral density, TBS and body composition parameters were measured using DXA. Results: AP presented with lower TBS compared to CON (1.2 ± 0.1 v 1.31 ± 0.1, P< 0.001). No significant correlation was observed between IGF-1/GH levels and TBS. Age, glycated haemoglobin, BMI, waist circumference, fat mass, and lean mass negatively correlated with TBS in both sexes. Multiple linear regression analysis of all these parameters revealed age and waist circumference as independent significant predictors of TBS in AP. We did not find difference in BMD (lumbar and femoral sites) between AP and CON nor between active and controlled AP. We observed negative correlation between age and BMD of the femoral neck and total hip (P < 0.001). Testosterone levels in males, BMI, waist circumference, fat mass, and lean mass positively correlated with BMD in AP, with stronger correlation between lean mass and BMD compared to fat mass. Conclusion: Patients with acromegaly have lower TBS than controls, confirming impaired bone microarchitecture in acromegaly regardless of BMD. Age, body composition parameters and glucose metabolism contribute to TBS deterioration in AP more than disease activity itself.

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.

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.

Adiponectin/leptin ratio as a predictor of acute rejection in early post-transplant period in patients after kidney transplantation.

Introduction: Adipokines are largely involved in the regulation of immune system activity. While leptin is the main pro-inflammatory marker of adipose tissue, adiponectin is characterized by anti-inflammatory effects. The aim of our study was to determine the risk of acute graft rejection in protocol biopsy depending on the adiponectin/leptin (A/L) ratio in patients after kidney transplantation (KT). Materials and methods: A total of 104 patients were included in the prospective analysis, in whom the levels of adipokines were examined pre-transplant, in the 3rd month after KT and the A/L ratio was calculated. In the 3rd month after KT, all patients underwent protocol biopsy of the graft and examination of donor-specific antibodies (DSA) using the Luminex method. Results: After adjusting for differences in the basic characteristics of the donor and recipient, we identified a subgroup with A/L ratio < 0.5 pre-transplant [HR 1.6126, (P = 0.0133)] and 3 months after KT [HR 1.3150, (P = 0.0172)] as independent risk factor for acute graft rejection. In the subsequent specification of the rejection episode, we identified the risk ratio A/L < 0.5 before KT [HR 2.2353, (P = 0.0357)] and 3 months after KT [HR 3.0954, (P = 0.0237)] as independent risk factor for the development of acute humoral rejection with DSA positivity. Conclusion: This is the first study to investigate the relationship between A/L ratio and immunological risk in terms of the development of rejection changes in patients after KT. In our study, we found that A/L ratio < 0.5 is an independent risk factor for the development of acute humoral rejection and de novo DSA production in the third month after KT.

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.

Filling the gap between the heart and the body in acromegaly: a case-control study.

OBJECTIVE: Cardiovascul diseases are the most common comorbidities in acromegaly. Potential parameters in pathology of cardiovascular comorbidities are changes in levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) as well as body composition parameters. PURPOSE: The aim of this study was to examine morphological and functional parameters of the cardiovascular system by echocardiography and to assess its relationship with disease activity and body composition parameters. METHODS: We prospectively enroled 129 acromegalic patients (82 females, 47 males) and 80 healthy controls (53 females, 27 males) matched for age, gender, and BMI. All patients underwent two-dimensional echocardiography. Body composition parameters were assessed by dual-energy X-ray absorptiometry. RESULTS: Acromegaly patients presented with higher left ventricle mass (LVM) compared to controls (LVMI: 123 ± 45 g/m2 vs 83 ± 16 g/m2, P < 0.001). Prevalence of left ventricle hypertrophy in acromegaly patients was 67% (78% concentric, 22% eccentric). IGF -1 levels, BMI, and lean mass positively correlated with LVM in all acromegaly patients (P < 0.001). Fat mass positively correlated with LVM in females (R = 0.306, P = 0.005), but this correlation was not found in males. We did not find any difference in size of the left and right ventricle between acromegaly patients and controls. Acromegaly patients presented with left atrium enlargement, diastolic dysfunction and low incidence of systolic dysfunction. Valvopathy was found in 43% of patients with predominant (31%) prevalence of mitral regurgitation. CONCLUSION: Our study demonstrates higher prevalence of cardiovascular comorbidities in acromegaly patients and the impact of IGF-1 levels and body composition parameters in pathology in some of these comorbidities.

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.

Pegvisomant in the treatment of acromegaly.

Despite improvements in surgical techniques, current radiotherapy options and development of long-acting somatostatin analogues, biochemical control of acromegaly is not achieved in some patients. The failure to achieve optimal serum growth hormone (RH) and insulin-like growth factor-1 (IGF-1) levels means increased morbidity and mortality of acromegaly patients. The RH receptor antagonist pegvisomant (PEG) is a genetically engineered RH analog that prevents of RH receptor dimerization, i.e. a process that is crucial for the action of RH at the cellular level. The effect of the treatment is suppression of IGF-1 production. In pilot studies, normalization of IGF-1 levels was achieved in up to 90 % of patients receiving PEG. However, PEG efficacy in clinical settings is slightly lower (65 to 97 %) than reported in the key studies. A rare side effect of treatment is elevations of liver transaminases. In addition, pituitary tumor growth progression has been reported in several cases. In this review article, we present long-term data on pegvisomant treatment and discuss its associated risks and benefits.

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.

Changes in Cross-Sectional Area of the Median Nerve and Body Composition Parameters after Treatment of Acromegaly: 1 year Follow-Up.

Objective: Median neuropathy is a common manifestation of acromegaly, although its pathology is uncertain. Changes in levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) and body composition are potential parameters in pathology of median neuropathy in acromegaly. We aimed to assess changes in the cross-sectional area (CSA) of the median nerve and body composition in newly diagnosed acromegalic patients 1 year after treatment and to determine their mutual relationships. Design: This prospective study included 30 patients with newly diagnosed acromegaly and 30 healthy controls matched for age, gender, and body mass index. Physical and laboratory examinations, dual-energy X-ray absorptiometry (DXA), and ultrasound evaluations were performed at baseline and 1 year after initial treatment. Results: The CSA of the median nerve was increased in acromegalic patients compared with controls (13.1 mm2 [12.2-14.9] vs 7.5 mm2 [6.4-8.4], P < 0.001). One year after treatment of acromegaly, GH and IGF-I levels decreased significantly. The median nerve CSA was significantly reduced after treatment (11.6 mm2 [10.2-13.1], P < 0.001). Reduction of IGF-I levels correlated with a decrease in lean mass and increase in fat mass. The median nerve CSA positively correlated with IGF-I levels (R = 0.492, P=0.006) and lean mass (R = 0.419, P=0.021) in acromegalic patients before treatment. Conclusion: This study demonstrates a reduction in the median nerve CSA 1 year after treatment of acromegaly. These changes are closely associated with a reduction in IGF- I levels and in lean body mass. The enlargement of the median nerve in acromegaly can be reversed with adequate treatment.

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.

Rotational thromboelastometry in patients with type 2 diabetes and mild COVID-19 pneumonia: A pilot prospective study.

BACKGROUND: It was repeatedly demonstrated that patients with severe COVID-19 pneumonia, as well as patients with type 2 diabetes (T2D) have higher risk of thromboembolic complications. Rotational thromboelastometry (ROTEM®) is a viscoelastic hemostatic assay which allows complex assessment of hemostasis in whole blood. The aim of this study was to compare changes in hemostasis measured by ROTEM® in diabetic and nondiabetic patients with mild COVID-19 pneumonia. METHODS: We performed a pilot, prospective, observational study and enrolled 33 consecutive patients (14 with T2D and 19 nondiabetic ones) admitted to regular ward with mild COVID-19 pneumonia. The control group consisted from 11 healthy, nondiabetic blood donors. Blood samples were tested with ROTEM® using INTEM® and EXTEM® reagents. RESULTS: We detected significant differences in EXTEM® clotting time (CT), clot formation time (CFT), and maximum clot firmness (MCF) comparing patients with mild COVID-19 pneumonia and healthy donors. However, there were no significant differences in EXTEM®, INTEM®, and HEPTEM® parameters (CT, CFT, and MCF) according to diabetes status. CONCLUSIONS: Our study demonstrated hypercoagulation in patients with mild COVID-19 pneumonia. T2D did not affected ROTEM® parameters in patients with mild COVID-19 pneumonia.

Recurrent Ileal Variceal Bleeding as a Diagnostic and Therapeutic Challenge.

Introduction: Massive ileal variceal bleeding is a rare intricate condition that needs rapid management and treatment. The absence of randomized clinical trials in this field leads to a lack of evidence-based diagnostic and therapeutical approaches. We present a case report describing imaging, endoscopic, and surgical procedures leading to the diagnosis and resolution of severe ileal variceal bleeding. Case Report. We admitted a 63-year-old patient for recurrent anemia and ongoing bleeding from the gastrointestinal tract presenting as enterorrhagia. We were not able to elucidate the source by endoscopic, angiographic, or nuclear imaging methods. As a last resort, we carried out a surgical procedure with peroperative enteroscopy and subsequent resection of the affected part of the intestine. Conclusion: We present a patient with a case of ileal variceal bleeding, which required extensive diagnostic and therapeutic effort with a unique peroperative enteroscopic approach.