Background: Autoimmune polyglandular syndrome type II (APS II) is a rare, multifactorial disorder characterised by a combination of primary adrenal insufficiency with other autoimmune endocrinopathies, most commonly thyroid disease and type 1 diabetes mellitus. The clinical presentation is variable, and non-specific symptoms often lead to delayed diagnosis. Case description: We report the case of a 37-year-old female patient with a history of Graves-Basedow thyroid disease status post total thyroidectomy, admitted for dyspeptic symptoms, vomiting and severe hyponatraemia (112 mmol/l). Endocrinological evaluation revealed hypocortisolism with elevated adrenocorticotropic hormone (ACTH), reduced insulin, C-peptide and dehydroepiandrosterone sulfate (DHEAS) levels, and adrenal atrophy on MRI. Serological tests demonstrated IgA deficiency and positive anti-dsDNA antibodies of the IgM class. Additionally, the patient presented with bicytopaenia associated with autoimmune neutropaenia and detectable anti-granulocyte and anti-lymphocyte antibodies. The patient was diagnosed with APS II and started on hydrocortisone and fludrocortisone replacement therapy, resulting in subsequent clinical stabilisation. Conclusion: In this case, Addison’s disease represented the first clinical manifestation of APS II and presented with severe hyponatraemia. A rare aspect of this case was the presence of bicytopaenia with autoimmune neutropaenia, which is not a typical feature of APS II and thus expands its phenotypic spectrum. This case highlights the importance of early recognition of endocrine causes of severe hyponatraemia and demonstrates that APS II can also manifest with rare haematologic complications. Long-term follow-up is essential due to the risk of progression or the development of additional autoimmune disorders.

Obesity is a global health problem with numerous metabolic and mechanical complications. In previous studies, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has been identified as one of the most promising medications for treating obesity. We carried out a prospective observational study investigating the effect of submaximal doses of semaglutide in 56 adult patients with obesity (mean age 49 ± 12 years, 42 female and 14 male). We evaluated the effects on body weight, waist circumference, height/waist ratio, and BMI during 3-month follow-up. 30 patients in our group also reached a 6-month follow-up. Our patients achieved a weight loss of 6.45 ± 0.31% (p < 0.01) in 3 months of semaglutide therapy, and in the subgroup of 30 patients where semaglutide was administered for 6 months, weight loss was 11.35 ± 0.47% (p < 0.01). Regarding waist circumference, patients achieved a 7 cm decrease in waist circumference in 3 months, and an additional 6 cm at 6 months, respectively (p < 0.01). The mean height/waist ratio decreased from 0.71 ± 0.08 to 0.67 ± 0.09 after 3 months of treatment (p < 0.01) and to 0.63 ± 0.09 (p < 0.01) after 6-month of semaglutide treatment. Mean BMI decreased from 40.3 ± 6.7 to 37.5 ± 6.83 kg/m2 (p < 0.01) after 3 months of treatment and to 35.5 ± 7.73 kg/m2 in the subgroup with 6 months of therapy (p < 0.01). Our study showed a significant decrease in body weight, waist circumference, height/waist ratio, and BMI in patients with obesity treated with submaximal doses of semaglutide.

Tumour-induced hypoglycaemia is one of the rare causes of hypoglycaemia. The most common causes include endogenous hypersecretion of insulin by the B cells of the islets of Langerhans themselves—Islet Cell Tumour Hypoglycaemia (ICTH). However, some tumours can lead to paraneoplastic hypoglycaemia by the production of substances interfering with glucose metabolism—Non-Islet Cell Tumour Hypoglycaemia (NICTH). NICTH usually occurs in patients with solid tumours of mesenchymal or epithelial origin, less frequently with haematological and neuroendocrine tumours. Diagnosis of tumour-induced hypoglycaemia is often late and challenging as it may manifest several years after diagnosis and treatment of the tumour, but on the other hand, it may also precede the diagnosis of the tumour itself. Hypoglycaemia that is not associated with diabetes mellitus (DM) and/or its treatment is not a common clinical disorder Iglesias (Euro J Endocrinol 170:147–157, 2014), Mohammedi (Endocrinol Diabetes Metab, 2014), Groot (Endocrine-Related Cancer 14:979–993, 2007). In people without DM, hypoglycaemia is defined as a venous plasma glucose value of less than 3 mmol/l, which is accompanied by the Whipple triad: (1) clinical signs of hypoglycaemia, (2) low plasma glucose concentration, (3) resolution of symptoms after plasma glucose correction Iglesias (Euro J Endocrinol 170:147–157, 2014), Soutelo (Arch Endocrinol Metab 61: 98–102, 2017). Cancer is a rare cause of paraneoplastic hypoglycaemia Mohammedi (Endocrinol Diabetes Metab, 2014). Tumour-induced hypoglycaemia (TIH) is a rare cause of hypoglycaemia that can occur due to excessive or reduced insulin secretion. The pathogenic mechanisms include (1) hypersecretion of insulin by a pancreatic tumour of B cells in the islets of Langerhans—insulinoma (Islet Cell Tumour Hypoglycaemia—ICTH) or hyperplasia of B cells—nesidioblastosis (NIPHS – Non Insulinoma Pancreatogenous Hypoglycaemic Syndrome) or ectopic insulin production, (2) infiltration of the liver or adrenal glands by a tumour, and (3) production of substances that interfere with glucose metabolism in non-B cell (non-pancreatic) tumours (Non-Islet Cell Tumour Hypoglycaemia—NICTH), including antibodies against insulin receptors (e.g., in haematological malignancies). The pathogenetic mechanisms of TIH are listed in Table 1. The most common cause, although rare overall, is hyperinsulinemia due to a pancreatic B cell tumour (insulinoma). Table 1 Pathogenetic Mechanisms and Types of Tumours Associated with TIH (adapted from 1) Insulin-secreting tumours Eutopic Tumour Insulin Pancreatic Islet: B-cell Tumour (ICTH) Insulinoma Ectopic Tumour Insulin Secretion: Non-Islet-Cell Tumours (NICTH) Bronchial Carcinoid Gastrointestinal Stromal Tumour Squamous Cell Carcinoma of the Cervix Schwannoma Neurofibrosarcoma Paraganglioma Small Cell Carcinoma of the Cervix Mechanisms other than excess tumour insulin secretion Tumour IGF2 precursors secretion (big IGF2)—“IGF2-oma” Leiomyosarcoma Fibrosarcoma Adrenal carcinoma Desmoplastic small round cell tumour Hemangiopericytoma Pheochromocytoma Renal sarcoma Uterine leiomyoma Hepatocellular carcinoma Tumour somatostatin secretion “Somatostatinoma” Pancreatic neuroendocrine tumour Ovarian neuroendocrine tumour Tumour IGF1 secretion “IGF1-oma” Large cell carcinoma of the lung Tumour glucagon-like peptide 1 (GLP1) secretion “GLP1-oma” Ovarian neuroendocrine tumour Pancreatic neuroendocrine tumour Autoantibodies to insulin or its receptor “Tumour autoimmune hypoglycaemia” Other tumour-related factors Massive tumour burden Massive liver tumour infiltration Pituitary and/or adrenal glands tumour destruction

Background: Impaired endothelial function has been associated with vascular complications in type 2 diabetes (T2D), but its role in T2D-related heart failure (HF) remains indeterminate. The aim of this study was to assess selected markers of endothelial function in T2D patients with acute decompensated HF. Methods: A pilot prospective study on patients with acute decompensated HF requiring in-hospital admission was carried out. The vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were assessed at admission and after decongestion. Subsequently, differences in these markers between T2D and non-diabetic (ND) patients were studied. Results: In total, 39 patients (21 with T2D and 18 ND patients) were enrolled. Twenty-eight patients presented with preserved ejection fraction (EF), and 11 presented with reduced EF. Looking at the VEGF levels in T2D patients, on admission, a median of 233.0 pg/mL (1.7–598 pg/mL) was found compared to 106.0 pg/mL (1.7–888 pg/mL) in ND individuals; the differences reached statistical significance (p = 0.04). There were no significant differences in VEGF levels after decongestion, and in VCAM-1 (2237 ± 1195 vs. 2699 ± 1093 ng/mL, p = 0.37) and ICAM-1 (596 ± 268 vs. 638 ± 437 ng/mL, p = 0.79) levels between T2D and ND patients upon admission and after decongestion. The value of EF (preserved or reduced) affected the VEGF levels upon admission. Conclusions: This study identified significantly higher VEGF levels upon admission due to acute decompensated HF in T2D patients.

Background: Obesity is closely linked to metabolic dysfunction and systemic low-grade inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly utilized for obesity treatment due to their significant metabolic benefits, including weight loss and improved glycemic control. The aim of the study was to evaluate the effect of submaximal doses of long-lasting GLP-1RA semaglutide on selected biomarkers of obesity-related inflammation, adipocytokines levels and metabolism in a real-world population of obese patients. Methods: We performed a prospective, observational study involving 32 adult patients (11 men, 21 women; mean age 49 ± 12 years; BMI 40.5 ± 7.3 kg/m2) treated with submaximal doses of semaglutide over 12 weeks, together with hypocaloric diet and increased physical activity based. We analyzed selected biomarkers including insulin, leptin, ferritin, resistin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) before and after three months of treatment. Results: We observed significant reductions in weight, BMI, waist circumference, insulin and leptin levels (all p < 0.001). On the other hand, no significant changes were recorded in ferritin (p = 0.806), IL-6 (p = 0.607), TNF-α (p = 0.633), resistin (p = 0.250) or PAI-1 (p = 0.134) levels. Correlation analyses revealed the correlation between IL-6 and adiposity indices (BMI, waist circumference) both before and after treatment. Ferritin and PAI-1 levels positively correlated with waist circumference, while resistin showed a negative correlation with central obesity. Conclusions: Submaximal-dose GLP-1 RA therapy was associated with significant improvements in metabolic parameters and adipokine regulation, but did not affect systemic inflammatory markers within 12 weeks. Future studies with larger cohorts and longer follow-ups are needed to clarify the associations.

Reactive hypoglycemia (RH) is a heterogeneous clinical entity characterized by adrenergic and neuroglycopenic symptoms occurring 1–5 hours after food intake, most commonly following consumption of high-carbohydrate meals. RH can manifest in various forms, including alimentary, idiopathic, prediabetes/diabetes, hormonal, or secondary to congenital enzymatic defects. Pathophysiological mechanisms involve inappropriate insulin secretion, increased incretin response, impaired counter-regulatory hormone activity, or altered glucose metabolism. Diagnostic approaches include a 5-hour oral glucose tolerance test (oGTT) or mixed meal tolerance test (MMTT), although both can produce false-positive or false-negative results. Continuous glucose monitoring (CGM) may aid in detection. Clinical presentation varies from transient adrenergic symptoms to neuroglycopenic signs, and in rare cases, chronic fatigue or mood disturbances. Differential diagnosis must exclude insulinoma, dumping syndromes, and pseudo-hypoglycemia related to adrenergic hyperreactivity or psychiatric factors. Management begins with dietary modification, favoring frequent small meals low in refined carbohydrates, and, when necessary, pharmacologic interventions such as alpha-glucosidase inhibitors, GLP-1 receptor modulators, or somatostatin analogues. In severe or refractory cases, invasive procedures including surgical revision of bariatric procedures may be considered. Awareness of RH and individualized multidisciplinary care are essential, especially in patients with risk factors such as insulin resistance, rapid gastric emptying, or endocrine disorders.

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.

Jurica, Jakub MD; Péč, Martin Jozef MD; Bolek, Tomáš MD, PhD; Škorňová, Ingrid MSc, PhD; Staško, Ján MD, PhD; Galajda, Peter MD, PhD; Samoš, Matej MD, PhD, MPH; Mokáň, Marián MD, DSc, FRCP Edin Author Information

Aims: The aims of this study were to compare global longitudinal strain of the left ventricle (LV-GLS) and reservoir strain of the left atrium (R-LAS) values between patients with acute decompensation of chronic heart failure (HF) and a control group. Methods: Sixteen patients admitted to our ward for acute decompensation of HF were enrolled in this study. Transthoracic echocardiography (TTE) with two-dimensional speckle-tracking analysis (2D ST) was performed in each patient. The patients were divided into two subgroups according to the value of left ventricular ejection fraction (EF) using a cut-off value of ≤40% to distinguish heart failure with reduced ejection fraction (HFrEF) from heart failure with preserved ejection fraction (HFpEF). The control group consisted of 16 individuals without a history of cardiovascular disease, each of whom underwent 2D ST analysis as well. Results: We found that LV-GLS and R-LAS were significantly lower in both the HFrEF and HFpEF subgroups in comparison with the control group (LV-GLS: −13.4 ± 4.7% vs. −19.7 ± 2.5%, p ˂ 0.05; R-LAS: +12.2 ± 6.9% vs. +40.3 ± 7.4%, p ˂ 0.05). Furthermore, there was a significant difference in LV-GLS (−9.6 ± 3.2% vs. −15.2 ± 4.3%, p ˂ 0.05) but not in R-LAS (+13.7 ± 8.6% vs. +11.4 ± 6.2%) between the HFrEF and HFpEF subgroups. Conclusions: Our study demonstrated a significant difference in LV-GLS and R-LAS in all enrolled HF patients compared to the control group. There was also a significant difference in LV-GLS between the HFrEF and HFpEF subgroups.

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.

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.

Objectives The aim of this article is to provide an insight into the role of obesity as a risk factor, and as a potential etiologic agent of atrial fibrillation (AF) and heart failure (HF). Methods A narrative (non-systematic) review article summarizing currently available data regarding the interaction between obesity, AF and HF. Results Obesity is considered a risk factor of AF and chronic HF. Multiple recent studies indicate that obesity is also a potential causal factor in the development of AF and HF, the elucidation of pathological mechanisms of which could help devise new diagnostic and therapeutic modalities for these conditions. The discussion about obesity in relation to HF cannot omit the so-called obesity paradox, which represents a dilemma for clinicians, and it is still a source of irregularities regarding the strategy of weight reduction in obese patients with HF. Recently, the obesity paradox has also been assumed to play a role in the relationship between obesity and thromboembolic complications of AF. Conclusions Obesity is an independent and modifiable risk factor for AF and HF. In addition, there is an increasing volume of experimental and clinical data that suggests an important role of the epicardial adipose tissue in the pathophysiology of AF. However, several issues, such as the issue of optimal pharmacotherapy and weight reduction strategy in obese patients with HF remains still unanswered, and open for future investigation.

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.

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.

Samoš, Matej MD, PhD1; Bolek, Tomáš MD1; Škorňová, Ingrid PhD2; Benko, Jakub MD1; Stančiaková, Lucia MD, PhD2; Grilusová, Kristína MD1; Galajda, Peter MD, PhD1; Stasko, Ján MD, PhD2; Kubisz, Peter MD, DSc2; Mokáň, Marián MD, DSc, FRCP Edin1 Author Information

Introduction: Coronary artery embolism is a rare cause of acute myocardial infarction. We present a case of coronary embolism causing extensive anterolateral ST elevation myocardial infarction (STEMI) after an elective replacement of a cardiac resynchronization therapy/defi brillator (CRT-D) electrode. Case presentation: A 72-year-old male with atrial fi brillation was admitted for an elective reposition/replacement of CRT-D electrode. Anticoagulation was stopped before the procedure. After the procedure the patient developed sudden chest pain, dyspnea, and worsening of vital signs. These were accompanied by extensive ischemic anterolateral ECG changes and corresponding regional wall motion abnormalities. The urgent coronary angiography showed embolic distal occlusion of left anterior descending coronary artery. Conclusion: We present a rare, well-documented case report of coronary embolism complicating CRT-D electrode replacement. Kľúčové slová: CRT-D Fibrilácia predsiení Koronárna embolizácia STEMI

INTRODUCTION:Kidney transplantation is now a routine method used to treat end-stage renal disease. About 10 % of kidney transplant patients are patients with autosomal dominant polycystic kidney disease (ADPKD). After successful kidney transplantation, recurrent urinary tract infections also occur in initially asymptomatic patients.MATERIAL AND METHODS:The group included 320 patients after kidney transplantation. We compared patients with ADPKD versus patients without ADPKD in terms of the presence of recurrent urinary tract infections.THE RESULTS:The incidence of recurrent urinary tract infections (rIMCs) was 18% in patients without ADPKD and 48% in patients without ADPKD. Nephrectomy after kidney transplantation due to recurrent urinary tract infections eliminated this infectious complication (in 86% of patients).CONCLUSION:Kidney transplant patients with ADPKD have a significantly higher incidence of recurrent urinary tract infections. Removal of polycystic kidneys is a suitable solution if the infection persists.

Diabetes is associated with several diabetic-related abnormalities which increase the risk of onset or worsening of heart failure. Recent studies showed that the majority of diabetic patients present with heart failure with preserved ejection fraction (HFpEF), and the prevalence of HFpEF in diabetics is alarming. Moreover, outcomes in HFpEF are poor and could be compared to those of heart failure with reduced ejection fraction (HFrEF), with 1-year mortality ranging between 10 and 30%. In contrast to HFrEF, there is very limited evidence for pharmacologic therapy in symptomatic patients with preserved ejection fraction, and therefore, the optimal selection of treatment for diabetic HFpEF remains challenging. This narrative review article summarizes the currently available data on the pharmacological treatment of HFpEF in patients with diabetes.

Abstract: Patients with atrial fibrillation (AF) on long-term direct oral anticoagulants (DOACs) may be at higher risk of bleeding because of higher anti-Xa or anti-IIa levels. However, there is no postmarketing study investigating these DOAC plasma levels at the time of bleeding. The aim of this study was to evaluate DOAC levels at the time of a bleeding emergency. We analyzed 5440 patients examined at our Emergency Department in from April 1, 2019, to September 30, 2019. During this period, we prospective identified 105 consecutive patients with bleeding while on long-term antithrombotic therapy; 49 patients had AF on DOACs. We compared DOAC levels in patients who bled against a control sample of 55 patients who tolerated long-term high dose DOAC therapy without any emergency. Samples of these patients were tested with drug-specific anti-Xa chromogenic analysis (rivaroxaban and apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Dabigatran-treated patients who bled had significantly higher anti-IIa levels when compared with trough (261.4 ± 163.7 vs. 85.4 ± 57.2 ng/mL, P < 0.001) and peak samples of controls (261.4 ± 163.7 vs. 138.8 ± 78.7 ng/mL, P < 0.05). Similarly, there were significantly higher anti-Xa levels in rivaroxaban-treated and apixaban-treated patients with bleeding compared with trough control samples (rivaroxaban: 245.9 ± 150.2 vs. 52.5 ± 36.4 ng/mL, P <0.001 and apixaban: 311.8 ± 142.5 vs. 119.9 ± 81.7 ng/mL, P < 0.001), as well as in apixaban-treated patients when compared with peak control samples (311.8 ± 142.5 vs. 210.9 ± 88.7 ng/mL, P < 0.05). Finally, rivaroxaban anti-Xa levels in patients who bled tended to be higher compared with peak control samples (245.9 ± 150.2 vs. 177.6 ± 38.6 ng/mL, P = 0.13). This observational study showed a significant difference in anti-IIa and anti-Xa plasma levels in patients with AF with bleeding complications compared with those who tolerated long-term high-dose DOAC therapy without bleeding complications.