Search

Vascular malformations are present in a great variety of congenital syndromes, either as the predominant or additional feature. They pose a major challenge to the clinician: due to significant phenotype overlap, a precise diagnosis is often difficult to obtain, some of the malformations carry a risk of life threatening complications and, for many entities, treatment is not well established. To facilitate their recognition and aid in differentiation, we present a selection of notable congenital disorders of vascular system development, distinguishing between the heritable germinal and sporadic somatic mutations as their causes. Clinical features, genetic background and comprehensible description of molecular mechanisms is provided for each entity.

Probiotics are defined as live microorganisms that have a beneficial effect on health by exhibiting quantitative and qualitative effects on intestinal microflora and/or modification of the immune system. A strain is consid�ered probiotic if it demonstrates a series of clinically proven health benefits. In recent years, the number of studies related to the antioxidant properties of probiotics has significantly increased. Antioxidants are substances that inhibit the degree of oxidation of molecules and cause the transformation of radicals into inactive derivatives. The incorrect or inefficient antioxidant mechanisms results in oxidative stress and may occur in the course of many diseases such as diabetes, atherosclerosis, inflammatory bowel disease or damage to the heart, brain or transplanted organs. Correct functioning of antioxidant mechanisms seems to be crucial for the proper function�ing of our body; therefore, probiotics should be carefully investigated for potential antioxidant properties.

IntroductionDespite the common occurrence of streptokinase-induced hypotension among patients with acute myocardial infarction, the underlying pathophysiology remains obscure and poorly understood. Our study aimed to pool clinical evidence on the potential mechanism of streptokinase-induced hypotension through a systematic review of the literature.Material and methodsWe conducted literature search from Medline, Scopus and Web of Science on clinical studies related to streptokinase-induced hypotension.ResultsOur search yielded 972 citations. After removal of duplicates, 878 articles were screened for eligibility, of which 856 papers were excluded due to various reasons. Of the remaining 22 articles retrieved with full texts, eight relevant articles were selected for final analysis. Three themes emerged as the proposed mechanisms of streptokinase-induced hypotension, including (i) reduction in total peripheral resistance, (ii) complement activation, and (iii) dismissal of hypotheses involving other intermediaries.ConclusionsOur findings suggest that the underlying mechanism of streptokinase-induced hypotension lies primarily in the reduction in total peripheral resistance.

Empagliflozin is a SGLT2 inhibitor that has shown remarkable cardiovascular and renal activities in patients with type 2 diabetes (T2D). Preclinical and clinical studies of empagliflozin in T2D population have demonstrated significant improvements in body weight, waist circumference, insulin sensitivity, and blood pressure – effects beyond its antihyperglycaemic control. Moreover, several studies suggested that this drug possesses significant anti-inflammatory and antioxidative stress properties. This paper explores extensively the main preclinical and clinical evidence of empagliflozin administration in insulin resistance-related disorders beyond a diabetic state. It also discusses its future perspectives, as a therapeutic approach, in this high cardiovascular-risk population.

The assumption that light cigarette smoking, meaning smoking one to five cigarettes per day, is not so harmful has been dissipated by several studies. Regardless of the quantity of tobacco cigarettes, smoking remains a leading risk factor for the development and progression of cardiovascular diseases. Smoke is a mixture of several toxic chemicals, such as nicotine, carbon monoxide, and oxidants, implicated in the pathogenesis of cardiovascular and pulmonary diseases. Despite anti-smoking campaigns, a misconception concerning “safe smoking” still exists. The purpose of this literature review is to highlight the deleterious effect of light cigarette smoking and claim the consensus that there is no safe smoking.

Acute decompensated heart failure (ADHF) is a common clinical problem associated with a high mortality rate. Because ADHF has various aetiologies, there are a range of therapeutic options, among others, positive inotropes (inotropic drugs). As an inotropic agent whose mechanism is different than that of “classical” medicines, levosimendan (LSM) is one of the most common therapeutic options. Despite many publications on LSM, some issues related to its application remain unclear. The authors of this paper have attempted to summarise expert recommendations and reports available in the literature.

Flavonoids are a large class of compounds that are widely found in many plants, including plants used in Chinese herbal medicines. Previous studies have revealed that flavonoids possess biomedical activities, including antioxidant, anti-cancer, anti-viral, and anti-inflammatory properties. They also have the functions of lowering lipids, lowering blood sugar, and improving insulin resistance. This article selects four typical compounds of flavonoids, namely baicalin, baicalein, quercetin, and rutin, and reviews their effects and mechanisms of action in improving insulin resistance. With a view for future clinical research on flavonoids as antidiabetic drugs, we therefore provide the theoretical basis for the development and application of flavonoids.

Almost two decades ago strain and strain rate imaging were proposed as a new, potentially more sensitive modality for quantifying both regional and global myocardial function. Until now, however, strain and strain rate imaging have been slow to be incorporated into everyday clinical practice. More recently, two dimensional strain has been claimed as of greater clinical utility, given that it is angle independent, with improved feasibility and reproducibility as compared to tissue Doppler strain. Nevertheless, speckle tracking strain is reliant on 2D image quality and frame rates. Three dimensional speckle tracking could eliminate the problem of through-plane motion inherent in 2D imaging, but 3D strain is currently limited by low frame rates. Another limitation of strain imaging is that the results are dependent on the ultrasound machine on which analyses are performed, with variability in measurements between different vendors. Despite the diagnostic and prognostic advantages of 2D strain, there is a lack of specific therapeutic interventions based on strain and a paucity of long-term large-scale randomized trial evidence on cardiovascular outcomes. After overabundant literature the same definition of normal cut-off values is controversial and not univocal. Further studies are needed, involving both manufacturers and medical professionals, on the additive contribution, possibly different case by case, of interfering and artifactual factors, aside from myocardial function per se. These artifactual determinants and motion artifacts components could be dominant in individual cases and should always be taken into account in the clinical decision making process in a single case.

Urinary incontinence in the general population occurs in 7% of non-pregnant women under 39 years old, 17% of those 40 to 59 years old, and 23–32% of those over 60 years old. In athletes the prevalence is higher, especially in high-impact training and gravity sports. Pelvic floor muscles (PFM) have two important roles; they serve as the support for abdominal organs and are crucial for closure of the urethra, vagina and rectum. We present the proper mechanisms of PFM caudal contractions with proper abdominal muscle control to avoid excessive intra-abdominal pressure. Pelvic floor sonography is discussed as the only objective method for pelvic floor examination among sportswomen and a tool which should be used routinely by urophysiotherapists and urogynecologists. A multidisciplinary individualized approach to stress urinary incontinence among athletes is presented including: physiotherapy, diagnostic imaging, use of a pessary, tampons, pharmacologic and surgical treatment. We present guidelines for stress urinary incontinence treatment in sportswomen of different age.

Patients with type 2 diabetes are at high risk for cognitive decline and dementia. Despite the limited data on the possible pathogenetic mechanisms, evidence suggests that cognitive decline, and thus dementia and Alzheimer’s disease, might arise from a complex interplay between type 2 diabetes and the aging brain, including decreased insulin signalling and glucose metabolism, mitochondrial dysfunction, neuroinflammation, and vascular disease. Furthermore, there is increasing interest on the effects of antidiabetic agents on cognitive decline. There are many studies showing that antidiabetic agents might have beneficial effects on the brain, mainly through inhibition of oxidative stress, inflammation, and apoptosis. In addition, experimental studies on patients with diabetes and Alzheimer’s disease have shown beneficial effects on synaptic plasticity, metabolism of amyloid-, and microtubule-associated protein tau. Therefore, in the present review, we discuss the effects of antidiabetic agents in relation to cognitive decline, and in particular dementia and Alzheimer’s disease, in patients with type 2 diabetes.

Since their formal introduction in 1980, implantable cardioverter defibrillators (ICDs) have undergone innumerable design modifications through several generations. They are indispensable today in successfully managing fatal ventricular arrhythmias. Their role in averting sudden cardiac death is recognized beyond doubt. Their applications and indications have continuously expanded over the last two decades. This article reviews the salient features in the evolution of ICDs, their current indications, recent advances and future directions. With more advanced detection algorithms, the potential integration with leadless pacing, and the possibility to serve as a remote monitoring device to recognize atrial fibrillation, acute ischemia, or electrolyte imbalance, the application of ICDs is rapidly evolving.

IntroductionLipoprotein(a) (Lp[a]) is a risk factor of cardiovascular disease (CVD). Familial hypercholesterolemia (FH), which exhibits high low-density lipoprotein cholesterol (LDL-C) levels, is a risk factor of CVD. The relationship of Lp(a) with CVD has been characterized in populations specific to FH.Material and methodsStudies reporting on the relationship of Lp(a) with CVD among FH subjects via PubMed up to 2020 were reviewed.ResultsEight studies were identified as eligible. In the meta-analyses, a high Lp(a) level was significantly and predictively associated with CVD compared to a low Lp(a) level in 2 cross-sectional studies (odds ratio = 2.57; 95% confidence interval (CI): 1.16–5.73) and 6 cohort studies (risk/hazard ratio = 1.91; 95% CI: 1.50–2.43). The totally integrated relative risk of these studies was 1.97 (95% CI: 1.57–2.46).ConclusionsFH subjects with high Lp(a) levels can have a high CVD risk, and besides LDL-C, attention should be paid to Lp(a) levels in FH subjects.

Prostate cancer (PCa) is the most common cancer in men, with a steadily rising incidence, affecting on average one in six men during their lifetime. The increase in morbidity is related to the increasing overall life expectancy, prostate-specific antigen testing, implementation of new molecular markers for cancer detection and the more frequent application of multiparamet�ric magnetic resonance imaging. There is growing evidence demonstrating that active surveillance (AS) is an alternative to immediate intervention in patients with very low- and low-risk prostate cancer. Ongoing reports from multiple studies have consistently demonstrated a very low rate of metas�tases and prostate cancer specific mortality in selected cohorts of patients. As a matter of fact, AS has been adopted by many institutions as a safe and effective management strategy. The aim of our review is to summarize the contemporary data on AS in patients affected with PCa with the intention to present the most clinically useful and pertinent AS protocols.

The most widely accepted theory for the development of preeclampsia is the "two-stage theory". An imbalance between antiangiogenic and proangiogenic factors is considered the link between the two stages. Nowadays, an increasing amount of data is available on the use of measurements of serum concentrations of these factors in the prediction, diagnosis and management of preeclampsia. The most useful, modern biochemical test that may help in making crucial clinical decisions in patients with preeclampsia is the sFlt-1/PlGF (soluble fms-like tyrosine kinase 1/placental growth factor) ratio. The aim of this review is to present the current use of different biochemical tests in the prediction, diagnosis and management of preeclampsia. Development of these diagnostic methods in recent years and a belief in their ground-breaking role in modern management of preeclampsia make this review especially important.

The natural history of small renal masses (SRM) is still not well understood and they are frequently incidentally diagnosed in elderly patients. Therefore, there is a need for less invasive options sparing the patient from the side-effects related to conventional surgical treatment. PubMed and Medline database search was performed to look for new findings on active surveillance and focal therapy for SRM. Sixty-one articles published between 2002 and 2018 were selected for the purpose of the review. There is growing evidence confirming the safety of active surveillance in patients at surgical risk and there appears to be a satisfactory intermediate-term outcome of focal treatment of SRM. In the group of elderly patients with a decreased life expectancy active surveillance appears to be the most appropriate approach. The future of minimally invasive therapy appears bright, especially with the improvement of new imaging modalities.

Coronary heart disease is a common diseases of atherosclerosis. Despite the development of noninvasive therapies and the advancement of pharmacological methods and extensive drug regimens, coronary artery bypass grafting surgery is still the ultimate treatment option in many patients. Among the various complications following open heart surgery, one of the common difficulties is pulmonary complications associated with subsequent morbidity and mortality, which should be studied according to preoperative, perioperative, and postoperative factors. Preoperative factors include genetics, age, family history of pulmonary disease, smoking, coexisting disease, etc. Perioperative factors include surgical procedures like sternotomy incision, cardioplegia, and internal mammary artery harvesting; anaesthesia procedure effects like pulmonary collapse, maintenance drugs and morphine administration; and cardiopulmonary bypass pump by systemic inflammatory response syndromes. And finally, postoperative factors, especially mediastinitis and the role of nursing in the intensive care unit. Pulmonary complications after cardiac surgery include atelectasis, pleural effusions, pneumonia, pulmonary oedema, cardiogenic pulmonary oedema, acute respiratory distress syndrome, pulmonary embolism, phrenic nerve injury, pneumothorax, sternal wound infection, and mediastinitis, with different outbreaks in patients reported. Although the preoperative, perioperative, and postoperative factors play an important role in the occurrence of these complications, the preoperative factors, as factors that can be adjusted, should be considered more than the others and explained to the patient, and the preoperative patient’s assessment should be noted. Also, postoperative care with the goal of reducing infections and pulmonary complications should be addressed by the nursing team.

Hypopituitarism in neonates is rare, but has life-threatening complications if untreated. This review describes the features of hypopituitarism and the evidence for which infants in whom a genetic cause should be suspected. Importantly, neonates are often asymptomatic or present with non-specific symptoms. Hypopituitarism can be due to abnormal gland development as a result of genetic defects, which result from mutations in gene coding for transcription factors which regulate pituitary development. The mutations can be divided into those causing isolated hypopituitarism or those causing syndromes with associated hypopituitarism. The latter involve mutations in transcription factors which regulate pituitary, as well as extra-pituitary development. There is a paucity of evidence as to which patients should be investigated for genetic mutations, but detailed clinical and biochemical phenotyping with magnetic resonance imaging of the pituitary gland could help target those in whom genetic investigations would be most appropriate.

Innate lymphoid cells (ILCs) are a recently described group of immune cells that can regulate homeostasis and protect mammalian organisms, including humans, from infections and diseases. Considering this, ILC research is still ongoing to better understand the biology of these cells and their roles in the human body. ILCs are a multifunctional group of immune cells, making it important for the medical community to be familiar with the latest research about the ILC families and their functions in selected disease states, such as cancer formation, metabolic disorders and inflammation. By discovering the roles of ILC populations and their participation in many disorders, we can improve disease diagnostics and patient healthcare.

Ankyrins are adaptor molecules that in eukaryotic cells form complexes with ion channel proteins, cell adhesion and signalling molecules and components of the cytoskeleton. They play a pivotal role as scaffolding proteins, in the structural anchoring to the muscle membrane, in muscle development, neurogenesis and synapse formation. Dysfunction of ankyrins is implicated in numerous diseases such as hereditary spherocytosis, neurodegeneration of Purkinje cells, cardiac arrhythmia, Brugada syndrome, bipolar disorders and schizophrenia, congenital myopathies and congenital heart disease as well as cancers. Detecting either down- or over-expression of ankyrins and ergo their use as biomarkers can provide a new paradigm in the diagnosis of these diseases. This paper provides an outline of knowledge about the structure of ankyrins, and by making use of recent experimental research studies critically discusses their role in several health disorders. Moreover, therapeutic options utilizing engineered ankyrins, designed ankyrin repeat proteins (DARPins), are discussed.

As obesity becomes more common worldwide, the prevalence of obstructive sleep apnoea (OSA) continues to rise. Obstructive sleep apnoea is a well-known disorder that causes chronic intermittent hypoxia (CIH), which is considered a risk factor for atherosclerosis directly and indirectly. Ischaemic heart disease remains the leading cause of death. Most risk factors for atherosclerosis are well understood. However, other factors such as CIH are less well understood. Several studies have investigated the pathophysiology of CIH, attempting to uncover its link to atherosclerosis and to determine whether OSA treatment can be a therapeutic modality to modify the risk for atherosclerosis. In this article, we will review the pathophysiology of OSA as an independent risk factor for cardiovascular disease and discuss the most common markers that have been studied. We will also examine the potential impact of OSA management as a risk factor modifier on the reversibility of atherosclerosis.

Significant progresses have been made in adoptive cell therapy with CAR-T cells for cancers, especially for hematological malignancies. However, the treatment of solid tumors still poses a tremendous challenge and remains an unmet medical need. Several factors are held responsible for the inadequate responses: tumor heterogeneity, inefficient homing of T cells to tumor tissues, immunosuppressive microenvironment and the shortage of specific antigens shortage. Mesothelin is a cell-surface glycoprotein highly expressed in many types of solid tumors. As such, it has attracted much attention as a molecular target in cancer immunotherapy. Here, we delineate the barriers imposed by solid tumors on CARs, outline the rationale of mesothelin as a target for immunotherapy, summarize the preclinical and clinical results of mesothelin-targeted therapies, and extrapolate the expected results of CAR-T cells directed against mesothelin for solid tumors.

Coordinated medical care offered in Poland for patients suffering from neurofibromatosis type 1 and related RASopathies combines complex multispecialty consultation with permanent supervision and the patient’s oriented longitudinal care. Neurofibromatosis type 1 is one of the most common single gene disorders in the global population, observed in 1 out of 2500–3000 live births. It is a primary neoplasia disease with 100% penetration of the gene mutation but remarkable age-dependent onset of different disease signs and symptoms, outstanding clinical heterogeneity between patients even in one family and lack of genotype-phenotype correlation, a high rate of spontaneous mutation exceeding 50%, and multiple comorbidities among which increased risk of malignancy is the most important. Medical practice proved that not only patient-oriented complex but also coordinated care provided in centers of competence is indispensable for patients and the families and provides a sense of medical security to them in conjunction with public health costs rationalization.

Infection with hepatitis C virus (HCV) is a major health problem worldwide. A large proportion of perinatal HCV infections are silent and may present later in adulthood with long-term complications. HCV has no effective immune prophylaxis and hence appropriate follow-up of all infants born to HCV-infected mothers is necessary. Universal antenatal screening for HCV is largely debatable. Intrauterine and partum transmission of HCV are both possible and higher rates are associated with a high maternal serum viral load (> 106 copies per milliliter), concomitant HIV infection, prolonged or difficult delivery, and invasive fetal monitoring during delivery. Infection during pregnancy and infancy needs to be investigated more in order to design management strategies for perinatal transmission of HCV most effectively. The recently approved new-generation, oral, direct-acting antiviral drugs may open a new era in HCV therapy for pregnant women and infected infants if proved to be safe during conception and infancy.

miRNAs are small, non-coding RNAs, functioning as negative suppressors of target gene expression. A significant proportion of the transcriptome is subject to miRNA modulation. A single miRNA determines the expression of hundreds of genes, while miRNAs are relatively stable in biological fluids. Thus, they have attracted scientific interest regarding their use as biomarkers for several diseases. miRNA-375 mainly influences β-cell function and insulin secretion. Several studies, primarily experimental, have assessed its role as a biomarker in type 2 diabetes, while recently obtained human evidence supports this potential role. Besides its diagnostic potential, miRNA-375 may also have therapeutic implications. In view of the growing epidemic of type 2 diabetes, there is an unmet need for identification of biomarkers for early recognition and monitoring of these patients. Long-term, prospective human studies are required to elucidate whether miRNA-375 can evolve as a key player in diagnosis and prognosis of type 2 diabetes.

IntroductionTakayasu arteritis (TA) is a chronic vasculitis associated with an increased cardiovascular risk. The measurement of pulse wave velocity (PWV), carotid artery intima-media thickness (CIMT) and flow-mediated dilatation (FMD) are generally used for evaluating the cardiovascular risk. The application of these measurements to TA patients remains undetermined.Material and methodsClinical studies that reported the PWV, CIMT and FMD levels in TA patients, which were published prior to 2021, were summarized using PubMed.ResultsFifteen studies were eligible. Overall, in TA patients, the PWV and CIMT levels were significantly higher and the FMD levels were significantly lower compared to controls. Part of the studies showed that the disease activity of TA was significantly associated with the PWV, CIMT or FMD levels.ConclusionsThe PWV, CIMT and FMD measurements could be useful for evaluating the cardiovascular risk in TA patients. Further studies to determine the proper use of these measurements are warranted.

The outbreak of a newly identified coronavirus, the SARS-CoV-2 (alternative name 2019-nCoV), capable of jumping across species causing zoonosis with severe acute respiratory syndromes (SARS), has alerted authorities worldwide. Soon after the epidemic was first detected in the city of Wuhan in the Hubei Province of China, starting in late December 2019, the virus spread over multiple countries in different continents, being declared a pandemic by March 2020. The demographic characteristics of the infected patients suggest that age, sex, and comorbidities are predictive factors for the fatality of the infection. The mechanisms of viral entry into the human host cells seem to be in a close relationship with the mechanisms of regulating the renin-angiotensin system (RAS), which may explain the pathogenesis associated with the infection. This brings new insights into the possibilities of exploiting viral entry mechanisms to limit associated complications by means of enhancing the resistance of the infected patients using methods of regulating the RAS and strategies of modulating ACE2 expression. In this perspective article we exploit the mechanisms of COVID-19 pathogenesis based on the demographic characteristics of the infected patients reported in the recent literature and explore several approaches of limiting the initial steps of viral entry and pathogenesis based on viral interactions with ACE2 and RAS. We further discuss the implications of reproductive hormones in the regulation of the RAS and investigate the premise of using endocrine therapy against COVID-19.

Since epidemiological arguments favouring self-isolation during the COVID-19 pandemic are widely recommended, the consequences of social isolation/loneliness of older people considered to be at higher risk for severe illness are neglected. We identified and described medical, social, psychological, and religious issues, indirectly generated by the COVID-19 lockdown. Mortality induced by SARS-CoV-2 and death from other “neglected” issues were put in balance. Arguments for strict lockdown from most European countries are compared with a relaxed approach, as has been applied in Sweden. Social isolation affects disproportionally the elderly, transforming it into a public health concern. One witnesses openly ageist discourse, while painful decisions to prioritising ventilation for younger patients deepens the sense of hopelessness. Fear has led to anxiety disorders and depression. Various religious practices provide resources for coping with isolation/overcoming loneliness. Higher levels of mortality/morbidity due to “COVID-19 versus non-COVID-19” polarisation oblige the healthcare community to find ways to provide proper care for its elders.

Circulating concentration and activity of secretory phospholipase A2 (sPLA2) and lipoprotein-associated phospholipase A2 (Lp-PLA2) have been proven as biomarkers of increased risk of atherosclerosis-related cardiovascular disease (ASCVD). Lp-PLA2 might be part of the atherosclerotic process and may contribute to plaque destabilisation through inflammatory activity within atherosclerotic lesions. However, all attempts to translate the inhibition of phospholipase into clinically beneficial ASCVD risk reduction, including in randomised studies, by either non-specific inhibition of sPLA2 (by varespladib) or specific Lp-PLA2 inhibition by darapladib, unexpectedly failed. This gives us a strong imperative to continue research aimed at a better understanding of how Lp-PLA2 and sPLA2 regulate vascular inflammation and atherosclerotic plaque development. From the clinical viewpoint there is a need to establish and validate the existing and emerging novel anti-inflammatory therapeutic strategies to fight against ASCVD development, by using potentially better animal models and differently designed clinical trials in humans.

The progression of gonarthrosis results in reduction of physical activity. One of the factors that increase the risk of osteoarthrosis may be joint overload related to the malalignment of the mechanical axis of the lower extremity. The medial compartment (MC) of the knee is particularly susceptible to overload due to the external knee adduction moment (EKAM). Varus knee malalignment contributes to increased EKAM and thus results in increased MC loading. The purpose of this study is to present methods described in current literature aimed at reducing the disproportion in the distribution of loads on articular surfaces of medial and lateral knee compartments in people with varus knee malalignment. Methods have been divided into non-surgical (gait training, physiotherapy, and orthopedic supplies such as valgus braces, lateral wedge insoles, walking poles) and surgical ones (corrective osteotomy).

Non-alcoholic fatty liver disease (NAFLD) refers to fatty infiltration of liver in the absence of significant alcohol intake, use of steatogenic medication, or hereditary disorders. It is a common cause of chronic liver disease with a worldwide estimated prevalence ranging from 6.3% to 33%. The NAFLD is considered a hepatic manifestation of the metabolic syndrome. Insulin resistance and increased oxidative stress are central to pathogenesis of NAFLD, and risk factors include metabolic syndrome, diabetes mellitus, obesity, lack of physical activity, smoking, and high fat diet. NAFLD is associated with higher mortality as compared to the general population with cardiovascular disease being the most common cause of death. The NAFLD is associated with a higher prevalence of subclinical atherosclerosis as evidenced by odds of higher coronary artery calcification, higher average and maximum carotid intima-media thickness. It is also associated with stiff arteries as evidenced by higher cardio-ankle vascular index and higher brachial-ankle pulse wave velocity. Increasing evidence has linked NAFLD with atherosclerotic cardiovascular diseases. The NAFLD is associated with a higher prevalence of coronary artery disease (CAD), more severe CAD, poor coronary collateral development, and higher incidence of coronary events. The NAFLD is also associated with ischemic stroke. Studies have shown that the association between NAFLD and atherosclerotic cardiovascular diseases is independent of shared risk factors.

The direct oral anticoagulant rivaroxaban is useful in various indications that include venous deep vein thrombosis prophylaxis/treatment after knee/hip replacement surgery and prevention of stroke in patients with non-valvular atrial fibrillation. Its mechanism of action has been mostly associated with hemorrhage-related adverse effects; thus a number of non-hemorrhage-related adverse effects of the drug have received less attention or go unrecognized. These adverse effects mainly include liver injury, hypersensitivity reactions, leukocytoclastic vasculitis and hair loss. Clinicians should be aware of these rare adverse reactions and advise their patients to contact them as soon as they observe any unexpected clinical response.

Iron-overload syndromes may be hereditary or acquired. Patients may be asymptomatic early in the disease. Once heart failure develops, there is rapid deterioration. Cardiac hemochromatosis is characterized by a dilated cardiomyopathy with dilated ventricles, reduced ejection fraction, and reduced fractional shortening. Deposition of iron may occur in the entire cardiac conduction system, especially the atrioventricular node. Cardiac hemochromatosis should be considered in any patient with unexplained heart failure. Screening for systemic iron overload with serum ferritin and transferin saturation should be performed. If these tests are consistent with iron overload, further noninvasive and histologic confirmation is indicated to confirm organ involvement with iron overload. Cardiac magnetic resonance imaging is superior to other diagnostic tests since it can quantitatively assess myocardial iron load. Therapeutic phlebotomy is the therapy of choice in nonanemic patients with cardiac hemochromatosis. Therapeutic phlebotomy should be started in men with serum ferritin levels of 300 μg/l or more and in women with serum ferritin levels of 200 μg/l or more. Therapeutic phlebotomy consists of removing 1 unit of blood (450 to 500 ml) weekly until the serum ferritin level is 10 to 20 μg/l and maintenance of the serum ferritin level at 50 μg/l or lower thereafter by periodic removal of blood. Phlebotomy is not a treatment option in patients with anemia (secondary iron-overload disorders) nor in patients with severe congestive heart failure. In these patients, the treatment of choice is iron chelation therapy.

Hemorrhagic stroke, accounting for 10-30% of stroke cases, carries high rates of morbidity and mortality. This review presents the current knowledge on the efficacy of hyperbaric oxygen (HBO)-based modalities in the preclinical research on hemorrhagic stroke. Both preconditioning and post-treatment with HBO are considered as prospective therapeutic options. High efficacy of HBO therapy (HBOT) for brain hemorrhage has been noted. We found that moderate hyperbaric pressures appear optimal for therapeutic effect, while the therapeutic window of opportunity is short. HBO preconditioning offers more modest neuroprotective benefit as compared to HBO post-treatment for experimental intracerebral hemorrhage. We advocate for mandatory calculations of percent changes in the experimentally investigated indexes of HBO effectiveness and stress the need to design new clinical trials on HBO for hemorrhagic stroke.

Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in the RAS-MAPK (mitogen-activated protein kinase) signal transduction pathway are responsible for NS and other related disorders. Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients. Due to the high number of genes associated with NS and other RASopathy disorders, next-generation sequencing is the best choice for diagnostic testing. Patients with NS also have higher risk for leukemia and specific solid tumors. Age-specific guidelines for the management of NS are available.

Heart failure (HF) is one of the leading causes of morbidity, mortality, and health care expenditures in the US and worldwide. For three decades, the pillars of treatment of HF with reduced ejection fraction (HFrEF) were medications that targeted the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Prior attempts to augment the natriuretic peptide system (NPS) for the management of HF failed either due to lack of significant clinical benefit or due to the unacceptable side effect profile. This review article will discuss the NPS, the failure of early drugs which targeted the NPS as therapies for HF, and the sequence of events which led to the development of sacubitril plus valsartan (Entresto; LCZ696; Novartis). LCZ696 has been shown to be superior to the standard of care available for treatment of HFrEF in several substantial hard endpoints including heart failure hospitalizations, cardiovascular mortality, and all-cause mortality.

MicroRNAs (miRNAs, miRs) are short, non-coding molecules engaged in normal functioning of eukaryotic cells, as negative regulators of gene expression. Since the first discovery of miRNA in the early 1990s, hundreds of different miRNAs and their targets have been identified. A growing number of studies have aimed to search for microRNAs which have a key role in the regulation of insulin signaling and metabolic homeostasis. Recent evidence indicates that dysregulation of miRNA expression is involved in the development of various diseases, including type 2 diabetes mellitus (T2DM), obesity and cardiovascular diseases. This review summarizes the biogenesis of miRNAs and their role in pancreatic β cell biology, insulin signaling and metabolism. We also discuss recent findings of miRNAs associated with metabolic disorders and vascular diabetic complications, their diagnosis and therapeutic value. The PubMed database and published reference lists were searched for articles published between 1990 and 2016 using the following keywords: miRNA, miRNA and pancreas; miRNA and insulin; miRNA and type 2 diabetes mellitus, miRNA and obesity, and miRNA and microvascular or macrovascular diabetic complication. This review indicates that miRNA functioning is significantly different in metabolic diseases than in the normal condition.

Metastatic cancer, especially in the growing population of geriatric patients, presents a big challenge to these patients, as well as to treatment teams and the entire health care system. This article describes some common medical problems faced by patients with metastases to liver and bone, and presents a diagnostic approach, and therapeutic management of various symptoms, relevant to advanced stages of the malignant disease. The article highlights the importance of patient education on various aspects of metastatic cancer, and underscores the unique position of pharmacists practicing pharmaceutical care, which is particularly beneficial in this group of patients with advanced malignancy. Also, this paper emphasizes that achieving a proper balance between managing the malignant disease and maintaining the patients’ quality of life, especially in the elderly population, should involve coordinated efforts of the oncology treatment team, primary care physicians, pharmacists, therapists and nurses, as well as patients, their families and caregivers.

Cardiovascular disease is one of the main burdens of healthcare systems worldwide. Nevertheless, assessing cardiovascular risk in both apparently healthy individuals and low/high-risk patients remains a difficult issue. Already established biomarkers (e.g. brain natriuretic peptide, troponin) have significantly improved the assessment of major cardiovascular events and diseases but cannot be applied to all patients and in some cases do not provide sufficiently accurate information. In this context, new potential biomarkers that reflect various underlying pathophysiological cardiac and vascular modifications are needed. Also, a multiple biomarker evaluation that shows changes in the cardiovascular state is of interest. This review describes the role of selected markers of vascular inflammation, atherosclerosis, atherothrombosis, endothelial dysfunction and cardiovascular fibrosis in the pathogenesis and prognosis of cardiovascular disease: the potential use of cardiotrophin-1, leptin, adiponectin, resistin and galectin-3 as biomarkers for various cardiovascular conditions is discussed., CERO - CAREER PROFILE: Romanian researchers; European Social Fund Operational Programme Human Resources Development

Hypercholesterolemia is one of the main risk factors for coronary heart disease and significantly contributes to the high mortality associated with cardiovascular diseases. Statin therapy represents the gold standard in the reduction of low-density lipoprotein cholesterol concentration. Nevertheless, many patients still cannot achieve the recommended target levels, due to either inadequate effectiveness or intolerance of these drugs. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as a promising option in lipid-lowering treatment. After confirmation of their efficacy and safety in clinical trials, evolocumab and alirocumab received approval from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for introduction into clinical practice. In this review, we present a history of the development and mechanisms of action, as well as the results of the most important studies concerning PCSK9 inhibitors.

It is commonly considered that cognitive abilities decrease with age, especially with respect to processing and psychomotor speed. It is an interesting issue whether, apart from the ageing process, the undergoing of menopause itself deteriorates cognitive functions, compared to women at reproductive age. Hopes for improvement of cognitive functions were pinned on the use of menopausal hormone therapy. However, the results of studies concerning the effect of hormone replacement therapy on cognition proved to be contradictory. It seems that the essence of the problem is more complicated than only estrogen deficiency. It is suggested that estrogen receptor α (ERα) polymorphism may be responsible for the differences in the effect of estrogens on cognitive processes. The article presents current knowledge concerning the effect of estrogens on the central nervous system, especially the role of ERα polymorphism, with respect to foreseeing benefits from the use of exogenous estrogens for cognitive functions. At the present stage of research, ERα appears to be poorly specific; nevertheless, it may be an important instrument for the classification of peri- and post-menopausal patients in the group where therapy with the use of estrogens may bring about benefits in terms of prevention and treatment of cognitive disorders. It also seems necessary to conduct prophylactic, screening examination of cognitive functions in post-menopausal women, in order to identify those at risk of the development of dementia.

In light of the fact that the number of elderly citizens in society is steadily increasing, the search for dietary factors which might prolong mental agility is growing in significance. Coffee, together with its main ingredient, caffeine, has been the focus of much attention from various researchers, as data on its beneficial effects on human health continue to accumulate. Most reports indicate that moderate coffee consumption may in fact lower the risk for common neurodegenerative conditions, i.e. Alzheimer's and Parkinson's diseases. Regardless, due to their complex pathogenesis as well as methodology of scientific research, the exact impact of coffee consumption remains to be fully elucidated. At present, it seems safe to inform the general public that coffee drinkers need not fear for their health. Possibly, in the future experts will recommend drinking coffee not only to satisfy individual taste preferences but also to decrease age-related mental deterioration.

Underlying and precipitating causes of heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) should be identified and treated when possible. Hypertension should be treated with diuretics, angiotensin-converting enzyme (ACE) inhibitors, and β-blockers. Diuretics are the first-line drugs in the treatment of patients with HFrEF and volume overload. Angiotensin-converting enzyme inhibitors and β-blockers (carvedilol, sustained-release metoprolol succinate, or bisoprolol) should be used in treatment of HFrEF. Use an angiotensin II receptor blocker (ARB) (candesartan or valsartan) if intolerant to ACE inhibitors because of cough or angioneurotic edema. Sacubitril/valsartan may be used instead of an ACE inhibitor or ARB in patients with chronic symptomatic HFrEF class II or III to further reduce morbidity and mortality. Add an aldosterone antagonist (spironolactone or eplerenone) in selected patients with class II–IV HF who can be carefully monitored for renal function and potassium concentration. (Serum creatinine should be ≤ 2.5 mg/dl in men and ≤ 2.0 mg/dl in women. Serum potassium should be < 5.0 mEq/l). Add isosorbide dinitrate plus hydralazine in patients self-described as African Americans with class II–IV HF being treated with diuretics, ACE inhibitors, and β-blockers. Ivabradine can be used in selected patients with HFrEF.

Approximately 1% of the population suffers from rheumatoid arthritis (RA) worldwide (0.45% in Poland). The therapy consists of the use of disease-modifying antirheumatic drugs (DMARDs). Biologics are used in the form of the drug programme. Analysis of the NHF database demonstrated the sequence of conversion between drugs and time spent in a single treatment. In 2009, the patients would start the following treatments: adalimumab 5.8%; etanercept 14.4%; infliximab 23.1%; leflunomide 53.6%; rituximab 3%. After the first year 16% of patients changed therapy or abstained, and in the second year this situation affected 65% of patients. The following percentages maintained the same treatment in the last 6 years: infliximab 4%; adalimumab 15%; etanercept 21%; leflunomide on prescription was continued by 70%. Patients remain too long on the same therapy when it is inefficient. Achieving remission or low disease activity (DAS28 < 2.6) should take place within 6 months of starting therapy.

Rhabdomyolysis (RM), a fortunately rare disease of the striated muscle cells, is a complication of non-traumatic (congenital (glycogen storage disease, discrete mitochondrial myopathies and various muscular dystrophies) or acquired (alcoholic myopathy, systemic diseases, arterial occlusion, viral illness or bacterial sepsis)) and traumatic conditions. Additionally, RM can occur in some individuals under specific circumstances such as toxic substance use and illicit drug abuse. Lipid-lowering drugs in particular are capable of causing RM. This comprehensive review will focus on non-traumatic and non-drug-induced RM. Moreover, the pathology of RM, its clinical manifestation and biochemical effects, and finally its management will be discussed.

More than 5% of the world population lives with a hearing impairment. The main factors responsible for hearing degeneration are ototoxic drugs, aging, continued exposure to excessive noise and infections. The pool of adult stem cells in the inner ear drops dramatically after birth, and therefore an endogenous cellular source for regeneration is absent. Hearing loss can emerge after the degeneration of different cochlear components, so there are multiple targets to be reached, such as hair cells (HCs), spiral ganglion neurons (SGNs), supporting cells (SCs) and ribbon synapses. Important discoveries in the hearing regeneration field have been reported regarding stem cell transplantation, migration and survival; genetic systems for cell fate monitoring; and stem cell differentiation to HCs, SGNs and SCs using adult stem cells, embryonic stem cells and induced pluripotent stem cells. Moreover, some molecular mediators that affect the establishment of functional synapses have been identified. In this review, we will focus on reporting the state of the art in the regenerative medicine field for hearing recovery. Stem cell research has enabled remarkable advances in regeneration, particularly in neuronal cells and synapses. Despite the progress achieved, there are certain issues that need a deeper development to improve the results already obtained, or to develop new approaches aiming for the clinical application., Ministry of Economy and Competitiveness (Project CTQ2014-56611-R), Regional Government of Andalusia (Project P11-CTS-7651), Ramón Areces Foundation (Madrid, Spain)

Thyrotropin (TSH) is classically known to be regulated by negative feedback from thyroid hormones and stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. At the end of the 1990s, studies showed that thyrotroph cells from the pars tuberalis (PT) did not have TRH receptors and their TSH regulation was independent from TRH stimulation. Instead, PT-thyrotroph cells were shown to have melatonin-1 (MT-1) receptors and melatonin secretion from the pineal gland stimulates TSH- subunit formation in PT. Electron microscopy examinations also revealed some important differences between PT and pars distalis (PD) thyrotrophs. PT-TSH also have low bioactivity in the peripheral circulation. Studies showed that they have different glycosylations and PT-TSH forms macro-TSH complexes in the periphery and has a longer half-life. Photoperiodism affects LH levels in animals via decreased melatonin causing increased TSH- subunit expression and induction of deiodinase-2 (DIO-2) in the brain. Mammals need a light stimulus carried into the suprachiasmatic nucleus (which is a circadian clock) and then transferred to the pineal gland to synthesize melatonin, but birds have deep brain receptors and they are stimulated directly by light stimuli to have increased PT-TSH, without the need for melatonin. Photoperiodic regulations via TSH and DIO 2/3 also have a role in appetite, seasonal immune regulation, food intake and nest-making behaviour in animals. Since humans have no clear seasonal breeding period, such studies as recent ‘’domestication locus’’ studies in poultry are interesting. PT-TSH that works like a neurotransmitter in the brain may become an important target for future studies about humans.

The cardiac autonomic nervous system plays an important role in the genesis and maintenance of atrial fibrillation. Although, pulmonary vein isolation is the cornerstone in today’s approach to atrial fibrillation ablation, a considerable proportion of patients will recur with atrial arrhythmias following this procedure, especially in the non-paroxysmal forms. The pulmonary vein isolation indirectly targets and ablate the ganglionated plexi. This might ultimately enhance the efficacy of the procedure, but an optimal ablation strategy and a reliable method to confirm and quantify the efficacy of vagal denervation following the procedure might be necessary, thus leading to significantly better results.

Ultrasound prenatal examination enables one to assess the facial skeleton and the neck from the first weeks of gestation. Cervicofacial tumors detected via prenatal ultrasound are very rarely reported fetal pathologies. They include cystic hygromas, teratomas, epulides, vascular tumors, and thyroid tumors. The tumor category, its location and vascularization pattern allow one to accurately establish a diagnosis which is usually confirmed by clinical examination of the neonate or a pathological examination (surgical specimen, biopsy, autopsy). The prenatal ultrasound diagnosis of cervicofacial tumor in the fetus allows planning of pregnancy management and fetal therapy, preparation of the delivery, and perinatal as well as neonatal treatment.

Melanoma is one of the most dangerous and lethal skin cancers, with a considerable metastatic potential and drug resistance. It involves a malignant transformation of melanocytes. The exact course of events in which melanocytes become melanoma cells remains unclear. Nevertheless, this process is said to be dependent on the occurrence of cells with the phenotype of progenitor cells - cells characterized by expression of proteins such as nestin, CD-133 or CD-271. The development of these cells and their survival were found to be potentially dependent on the neural crest stem cell transcription factor SOX10. This is just one of the possible roles of SOX10, which contributes to melanomagenesis by regulating the SOX10-MITF pathway, but also to melanoma cell survival, proliferation and metastasis formation. The aim of this review is to describe the broad influence of the SOX10-MITF pathway on melanoma cells.