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Abstract Background Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are commonly coexisting clinical entities with still growing incidence worldwide. Recently, circulating microRNAs (miRNAs) have emerged as novel molecular players in cardiometabolic diseases. This study aimed to identify a specific miRNA signature as a candidate biomarker for CAD in T2DM and to delineate potential miRNA-dependent mechanisms contributing to diabetic atherosclerosis. Methods A total of 38 plasma samples from T2DM patients with and without CAD, CAD patients and healthy controls were collected for expression profiling of 2,578 miRNAs using microarrays. To investigate the regulatory role of differentially expressed (DE)-miRNA target genes, functional annotation and pathway enrichment analyses were performed utilizing multiple bioinformatics tools. Then, protein-protein interaction networks were established leveraging the STRING database in Cytoscape software, followed by cluster analysis and hub gene identification. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was carried out for microarray data validation in the larger replication cohort of 94 participants. Receiver operating characteristic analysis was applied to evaluate the diagnostic values of miRNAs. Multivariate logistic regression analysis was used to develop miRNA-based diagnostic models. Results In the discovery stage, overexpression of hsa-miR-4505, hsa-miR-4743-5p, hsa-miR-6846-5p, and down-regulation of hsa-miR-3613-3p, hsa-miR-4668-5p, hsa-miR-4706, hsa-miR-6511b-5p, hsa-miR-6750-5p, hsa-miR-4750-3p, hsa-miR-320e, hsa-miR-4717-3p, hsa-miR-7850-5p were detected in T2DM-CAD patients. The DE-miRNA target genes were significantly enriched in calcium ion binding, regulation of actin cytoskeleton, and gene expression. hsa-miR-4505, hsa-miR-4743-5p, and hsa-miR-4750-3p were found to be involved in fatty acid metabolism, leukocyte transendothelial migration, and neurotrophin signaling pathway. Dysregulation of hsa-miR-4505, hsa-miR-4743-5p, and hsa-miR-4750-3p in T2DM-CAD patients compared with T2DM subjects and controls (all p

Introduction: Pheochromocytomas are chromaffin cell tumours derived from the neural crest and they are associated with catecholamine production. Radiological procedures are playing essential role in present diagnostic of adrenal glands. Physicians who send their patients to the radiological examinations should prepare them to have a safe further diagnostic. Aa well radiologist should be aware of scanning protocols to provide best quality and the safest for the patient radiological examination.Aim of the study: This article summarizes the current knowledge about radiological imaging of pheochromocytomas and scan procedures. In this paper we also want to answer to the question does a patient with pheochromocytoma need to be specially prepared for radiological procedures.Description of knowledge: Diagnostic procedures play primary role in present diagnostic and treatment of pheochomocytomas. It is crucial for further diagnostic procedures to locate the tumour and its margins.Ultrasound imaging can be used with success only in big tumours with clinical symptoms. First choice for adrenal gland tumours is always CT. That modality easily shows localisation and tumours smaller than 1 cm. Another method of choice for adrenal imaging is MRI which gives high contrast images between soft tissues. Radiological differentiation of lessions wouldn’t be possible without contrast agents. They are crucial for calculations of washout in CT.Conclusions: Intravenous administration of non-ionic contrast agent for CT and gadolinium based in MRI is a safe practice for patients with pheos even without α-blocking medication. Only in an intra-arterial iodine-based contrast administration patient should be pharmacologically prepared before examination.

Introduction: Obesity is a chronic fatal disease with still growing incidence among children, adolescents, and adults worldwide. The subclinical inflammatory process together with hipoadiponectinemia may lead to the development of various comorbidities, including cardiovascular complications. That is why, the relationship between adipose tissue activity, obesity, insulin resistance, and endothelial function is in high interest and an object of extensively studies.Aim of the study: This article summarizes the current knowledge on the anti-atherogenic effects of adiponectin and its properties to improve endothelial function in obesity-related insulin resistance.Description of knowledge: Adiponectin, an adipose tissue-derived pleiotropic hormone with anti-inflammatory, anti-atherogenic, anti-diabetic, and insulin-sensitizing actions, is not only engaged in modulation of type 2 diabetes mellitus, hypertension or coronary artery disease, but the latest researches highlight its role in improving vascular wall integrity. It affects complex signaling pathways in endothelial cells and influence inflammatory responses in the subendothelial space. Pre-clinical and clinical studies suggest that agents leading to increase in adiponectin levels, simultaneously contribute to decrease insulin resistance, and improve endothelial dysfunction.Conclusions: Adiponectin may be a predictive factor of endothelial dysfunctionality and vascular remodeling development in the group of patients with overweight, obesity, and insulin resistance. Discovering pharmacological agents and non-pharmacological interventions that increase the level of circulating adiponectin will become novel and innovative therapeutic strategy to ameliorate obesity-related comorbidities. Therefore, further studies are required to determine the exact role of adiponectin in the pathogenesis of metabolic diseases.

It has been recently discovered that asprosin, an adopakine that is secreted by white adipose tissue, affects the release of glucose into the blood. When blood glucose levels rise, the production of asprosin is immediately suppressed. In healthy people, circulating asprosin shows daily fluctuations, and its concentration drops significantly with the beginning of eating. In patients with type 2 diabetes it was invastigated that both fasting and postprandial asprosin concentrations were significantly higher. Therefore, it is probable that elevated blood levels of asprosin and its impaired response to glucose levels fluctuation may be one of the causes of type 2 diabetes. It is considered, that administration of antibodies that block the action of asprosin may help diabetics reduce glucose levels. In addition, it can also contribute to the effective fight against obesity.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with still growing incidence among adults and young people worldwide. Patients with T2DM are more susceptible to developing coronary artery disease (CAD) than non-diabetic individuals. The currently used diagnostic methods do not ensure the detection of CAD at an early stage. Thus, extensive research on non-invasive, blood-based biomarkers is necessary to avoid life-threatening events. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that are stable in human body fluids and easily detectable. A number of reports have highlighted that the aberrant expression of miRNAs may impair the diversity of signaling pathways underlying the pathophysiology of atherosclerosis, which is a key player linking T2DM with CAD. The preclinical evidence suggests the atheroprotective and atherogenic influence of miRNAs on every step of T2DM-induced atherogenesis, including endothelial dysfunction, endothelial to mesenchymal transition, macrophage activation, vascular smooth muscle cells proliferation/migration, platelet hyperactivity, and calcification. Among the 122 analyzed miRNAs, 14 top miRNAs appear to be the most consistently dysregulated in T2DM and CAD, whereas 10 miRNAs are altered in T2DM, CAD, and T2DM-CAD patients. This up-to-date overview aims to discuss the role of miRNAs in the development of diabetic CAD, emphasizing their potential clinical usefulness as novel, non-invasive biomarkers and therapeutic targets for T2DM individuals with a predisposition to undergo CAD.

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with still growing incidence among adults and young people worldwide. Patients with T2DM are more susceptible to develop coronary artery disease (CAD) than non-diabetic individuals. Several pre-clinical and clinical studies suggested that adiponectin, a pleiotropic hormone with anti-atherogenic, anti-inflammatory, and insulin-sensitizing properties, may be a molecular link between metabolic and cardiovascular diseases. Aim of the study: This article summarizes the current knowledge on single nucleotide polymorphisms (SNPs) within the adiponectin and its receptors’ genes on the risk of CAD in patients with T2DM. Description of knowledge: Adiponectin, the most abundant circulating adipocytokine, is encoded by the Acrp30/adiponectin gene on chromosome 3q27, which constitutes a region specific for obesity-related metabolic syndrome. A genetic deficit of this adipokine may be responsible for the increased risk of CAD both in the general population and T2DM subjects. The results of recent years’ studies highlight that SNPs at the adiponectin locus, +45 T>G and +276 G>T as well within its two receptors, are determinants of early onset atherosclerosis in individuals with T2DM. Conclusions: SNPs in ADIPOQ, ADIPOR1 and ADIPOR2 may modify the risk of CAD in the group of patients with T2DM. SNP +45 and SNP +276 seem to be attractive, molecular markers for identification of diabetic individuals at especially high risk of CAD. The discovering of their exact mechanisms may result in novel screening options as well as diagnostic process and treatment scheme. Therefore, further research is required to determine the effects of adiponectin and its receptors’ polymorphisms and their roles in the pathogenesis of obesity-related metabolic diseases.

Introduction: is an endocrine gland located upon the hypophysial fossa of the sphenoid bone in the center of the middle cranial fossa and is surrounded by a small bony cavity (sella turcica). Radiological procedures are playing essential role in present diagnostic of pituitary gland. Pituitary tumours can now be visualized more accurately due to continued improvements in magnetic resonance imaging (MRI) techniques with gadolinium enhancement. Aim of the study: This article summarizes the current knowledge about radiological imaging of pituitary gland and in particular MRI scan procedures. In this paper we also want to show how the imaging of the pituitary gland looked like in the past and nowadays. Description of knowledge: Diagnostic procedures play primary role in present diagnosis and treatment of pituitary gland and sella turcica tumours. It is crucial for further diagnostic procedures to locate the tumour its size and margins. Currently magnetic resonance imaging is the more important examination just after the laboratory results. That modality easily shows exact location and tumours smaller than 1 cm. Radiological differentiation of lessions wouldn’t be possible without contrast agents. The latest MRI study protocols involve dynamic and delayed sequences for better visualisation and differential diagnostic. Conclusions: During the years radiological techniques evolved and gave us the perfect tool to visualize the pituitary gland and its pathologies.

Introduction: Hashimoto’s encephalopathy (HE) is a rare, potentially life-threatening disease with a wide spectrum of clinical manifestations from slight symptoms to mainly neurological and psychiatric syndromes, which significantly debilitate the quality of life and make the diagnostic process complicated, especially in patients with no previous history of thyroid disorders. According to the recent data, it occurs in about 2.1 cases per 100 000 population with still increasing prevalence. Despite, over than fifty years have passed since the first case of HE was reported, its etiopathogenesis is not completely clarify and there is no universal diagnostic criteria. Aim of the study: This article summarizes the current knowledge about pathophysiology, clinical manifestations, difficulties in differential diagnosis and therapeutic dilemmas in patients with HE. Description of knowledge: HE is an autoimmune-mediated encephalopathy associated with Hashimoto’s disease and elevated titers of anti-thyroid antibodies, mainly anti-thyroid peroxidase antibody. The diagnostic process is usually multi-step due to various diseases mimicking HE, such as Creutzfeldt-Jacob disease, brain tumors, epilepsy, Alzheimer's disease, stroke, other forms of autoimmune encephalitis, schizophrenia, spontaneous cerebrospinal fluid leak or infectious encephalitis. The range of diagnostic procedures includes physical and mental examination, laboratory tests, brain imaging, EEG as well as cerebrospinal fluid analysis. However, the first line strategy based on steroids is effective, there are some cases in the literature that reveal this management as not fully sufficient, because only partial improvement was achieved or the steroid-dependence was observed. Among other therapeutic methods, plasmapheresis may be used additionally. Conclusions: HE requires interdisciplinary approach and it constitutes a great challenge for clinicians of various specialties, such as endocrinologists, neurologists, and psychiatrists. The prompt implementation of adequate therapy usually provides the full recovery of the patients without any early or late complications.

Introduction: Autoimmune diseases constitute a significant clinical problem, due to the increasing incidence, that is why the potential causes that determine their occurrence are sought. Intestinal microbiota greatly outnumber the all of human body’s cells. Its metabolic activity and disorders in the structure, resulting from, for example, antibiotic therapy, lead to homeostasis dysregulation, and in this way gain a new meaning in the etiology of autoimmune diseases. Aim of the study: This article summarizes the current knowledge about gut microbiota in patients with autoimmune thyroid diseases as well as discussed the alterations in the gut microbiota and their potential relationship with thyroid cancer. Description of knowledge: The analyzed scientific literature revealed a relationship between the occurrence of autoimmune diseases and intestinal flora disorders. It is believed that the microbiota that colonized the entire human body, due to diversity, co-formation of the intestinal barrier, its own metabolic activity and participation in many metabolic processes, plays an important role in regulating the immune system functioning. Many data indicate, that the changes in the composition of the intestinal flora in many autoimmune diseases can also be influenced by individual factors, environmental conditions, genetic predisposition, and diet. Conclusions: Gut microbiota is an important element of the immune system and due to the demonstrated changes in its composition in various disease processes and its significant effects on metabolism, the researchers are still underway to clarify all pathogenetic mechanisms of microbiota influencing human homeostasis. Therefore, further studies are required to determine the effect of microbiota and its role in the pathogenesis of autoimmune diseases.

Introduction: Pheochromocytoma (PCC) is a very rare and life-threatening condition in pregnancy. According to different data, it occurs in about 0,00002%-0,007% of pregnant women. The early diagnosis and the proper clinical management play a crucial role in decreasing maternal and fetal mortality. Aim of the study: This article summarizes the current knowledge about the management with PCC in pregnancy and presents the possible maternal and fetal outcomes. Description of knowledge: The review revealed, that manifestations of catecholamine-secreting tumors are similar to the most common hypertension-associated problems occurring in pregnancy, such as pre-eclampsia. That is why, timely diagnosis is essential for the mothers and fetuses’ survivals. Despite the fact, that the fetus is protected from influence of maternal overproduction of catecholamines due to the presence of placental enzymes activity, there is an enormous risk of spontaneous abortion, fetal growth restriction, premature delivery, when the optimal therapy will not be applied on time. The diagnosis is based on laboratory tests – determination of plasma and urine concentration of catecholamines and imaging tests to localize the tumor, from which only MRI, in 1st and 3rd trimester, and ultrasound examination can be safely used in pregnancy. The guidelines suggest surgical tumor removal as the treatment of choice for women with PCC in pregnancy. The 2nd trimester seems to be the best period for the surgery, however it can be performed only after 10-14 days of effective therapy with alfa- and beta-blockers. The review of literature revealed that, surgical tumor removal carried out before the end of 24. hbd, is safe both for mother and her fetus life. Conclusions: PCC is a great challenge, because of the extremely rare occurrence in pregnant women and serious complications due to the secretion of catecholamines, which may result in catecholamin crisis, increasing the risk of mortality. Nevertheless, there is still no clear consensus on PCC treatment and further researches are needed to develop the optimal management in this clinical condition.

Introduction: Multiple myeloma (MM) is a hematological malignancy characterized by an abnormal proliferation and accumulation of monoclonal plasma cells. MM typically affects the elderly people with the median age at the diagnosis between 65 to 74 years. Only in < 2% of cases it is observed

Introduction: Pituitary adenomas are generally benign central nervous system neoplasms with still increasing prevalence, especially in younger people. According to the recent data, approximately 30-45% of them invade the local structures, which make their total resection impossible and result in high recurrence rate. Despite the huge advances in management with pituitary tumors, there are no universal biomarkers predicting their course. That is why, the two-way relationship between matrix metalloproteinases (MMPs) activities and the microenvironment of pituitary adenomas is an important object of extensive studies. Aim of the study: This article summarizes the current knowledge about selected MMPs and their tissue inhibitors (TIMPs) in tumorigenesis of pituitary adenomas as well as their role in local invasion in different hormonally active and inactive pituitary tumors. Description of knowledge: MMPs are a family of zinc-dependent proteolytic enzymes, which are engaged in various physiological and pathological conditions. So far, their role in different malignancies have been known for many years. Nevertheless, the possible effects of MMPs and TIMPs in pituitary adenomas are not fully understood. Recent studies suggested that MMPs’ expression is significantly higher in invasive pituitary tumors as compared to non-invasive pituitary adenomas, while the expression of TIMPs is decreased, which may prove their involving in tumorigenesis. Conclusions: MMPs may be predictive factors of the invasiveness and the higher recurrence rate in the group of patients with pituitary adenomas. Understanding the changes in the MMPs-TIMPs system and discovering of its exact mechanisms may result in applying novel screening options as well as modifying diagnostic process and treatment scheme. Therefore, further researches are required to determine the effects of MMPs and TIMPs and their role in the pathogenesis of invasive pituitary tumors.

Introduction: The aortic valve regurgitation (AR) is a heart defect consisting of the retrograde flow of blood from the aorta to the left ventricle due to the improper closure of the aortic valve leaflets. It occurs approximately in 13% of men and 8.5% of women, and the incidence increases with age. A crucial issue in regards to a patient with asymptomatic AR, especially of a high degree, is determination of the time of qualification for invasive treatment. Aim: To draw attention to the necessity of holistic approach to a patient with asymptomatic high-grade aortic regurgitation. Moreover, the complications of delayed implementation of invasive treatment were discussed. Case report: A clinical case of a 62-year-old patient with a history of coronary artery bypass grafting and with AR – stage II, accidentally detected two years later in a control echocardiogram, was presented. Despite gradual progress of regurgitation, none of the disturbing symptoms were noted, whereas cardiac parameters were systematically monitored using ECG, ECHO and CT imaging. Beta blockers, ACE inhibitors, loop diuretics and aspirin were used as conservative treatment. After 10-year transthoracic echocardiographic follow-up due to progression of AR and development of heart failure, the patient was qualified to surgical replacement of the aortic valve. This procedure significantly improved the patient's quality of life. Summary: The key element in the treatment of chronic asymptomatic AR is the individualization of the therapy. An essential role is played by appropriate pharmacotherapy, precise monitoring using transthoracic echocardiography, which is recommended as the first-line imaging strategy. Delaying in the implementation of surgical treatment may result in failure of the therapy and the onset of serious complications.

Introduction: Eosinophilia, defined as elevated level of eosinophils in peripheral blood above 5 x 109/L, is the hematological disorder, which may occur in multiple conditions, such as allergies, gastrointestinal, autoimmune diseases, parasite, fungal infections as well as drug related eosinophilia. Although hematological causes of eosinophilia (idiopathic, myeloproliferative and lymphocytic variant) should be taken into consideration. Aim of the study: The aim of our study was to performed the difficulties related to the differential diagnosis of eosinophilia, especially associated with the diverse symptoms. Materials and methods: The study included 5 patients hospitalized in the Department of Hematooncology and Bone Marrow Transplantation, due to eosinophilia associated with diverse symptoms. Medical history, physical examination, the peripheral blood as well as bone marrow samples analysis and the genetic tests for the presence of mutations or rearrangements that detect leukemia or lymphoma were analyzed. Moreover, patients were evaluated due to the presence of parasites. Results: The case series revealed that eosinophilia may have a various etiological background. Three patient demonstrated the reactive eosinophilia, caused by bacterial, parasite infections and eosinophilic granulomatosis with polyangitis, however in two other cases the chronic eosinophilic leukemia with abnormalities of PDGFRA were diagnosed. Conclusions: Eosinophilia is an important diagnostic and prognostic feature in a varied range of pathological conditions from infections, allergies to malignancies. For this reason, it is an enormous diagnostic as well as therapeutic challenge and requires an interdisciplinary clinical approach, especially in cases with unclear manifestations.

Introduction: Type 2 diabetes (T2DM) mellitus is the chronic, low-grade inflammatory disorder, which is considered to be the leading cause of morbidity and mortality worldwide. Wherefore, it is indispensable to look for new, non-invasive and widely available markers that will allow for early detection of predisposition to the development of diabetes as well as its macro- and microvascular complications. Aim of the study: The aim of our study was to present the role of white blood cells (WBC) count as a prognostic factor in type 2 diabetes mellitus. Moreover, we discussed the perspectives for the usefulness of WBC subtypes and neutrophil to lymphocyte ratio (NLR) as a marker of glycemic control as well as an indicator of the risk of developing diabetes complications. Description of knowledge: The abundant number of previous studies revealed that the elevated level of total WBC count strongly correlates with the predisposition to prediabetes and T2DM development. There is also association between the insulin resistance as well as the function and mass of beta-cells. The numerous research confirm that the increase in NLR may be the useful laboratory tool to evaluate the glycemic control and the effectiveness of antidiabetic treatment. NLR ratio as a marker, which directly reflects the level of inflammation is considered to indicate the risk of development of cardiovascular complications, diabetic peripheral neuropathy or nephropathy, even in the early stage of T2DM duration. Conclusions: Measurements of WBC count and changes in the number of subpopulations of them seem to be a useful, widely accessible marker of development of T2DM as well as its complications and may be helpful in management of T2DM patients.

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare, heterogeneous and life-threating disease requiring prompt differential diagnosis. The most common form of that disease is idiopathic form affects usually young adults. The etiopathogenesis is most likely based on the excessive formation of platelet aggregates and microthrombosis in small vessels, capillaries due to the deficiency of a specific enzyme, ADAMTS13 (disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Aim of the study: The aim of this review was to present the diagnostic difficulties of the TTP, which are mainly related to the range of multi-organ deficiency and symptoms that resemble lots of other diseases. Moreover, we discussed the current, as well as future perspectives of the treatment of thrombotic thrombocytopenic purpura. Description of knowledge: The principal symptoms, which occur in TTP patient are caused by microangiopathic hemolytic anemia and thrombocytopenia. Moreover, that disease may also manifest by neurological, renal, cardiac abnormalities as well as abdominal disturbances, fever and flu-like symptoms. The other thrombotic microangiopathies, especially hemolytic-uremic syndrome, immune-mediated diseases, infections, stroke, myocardial infarction should be taken initially in the differential diagnosis. The current management is based on plasma exchange therapy, steroids, rituximab, but the novel methods are investigated. Conclusions: The differential diagnosis of hematological patients presenting clinical symptoms of thrombocytopenia, anemia associated with multi-organ dysfunction, especially when we suspect an autoimmune background of a given disease is crucial to implement the appropriate therapy and save the patient's life.