Assessment of vascular damage in children and young adults with Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF) is the most frequent autoinflammatory disease. This study aimed to evaluate the risk of subclinical vascular damage in FMF children, and young adults, using both imaging and laboratory tests. Forty-five FMF patients (mean age 14.3 ± 9.5 years, 33 children) and 44 healthy controls(mean age 13.3 ± 8.6 years, 36 children) were included in the study. The patients were diagnosed according to Tel-Hashomer criteria, were positive for MEFV gene mutation, were treated with colchicine and were evaluated during an attack free-period. The arterial stiffness parameters studied were carotid-femoral pulse wave velocity (PWV), Augmentation Index (Aix), subendocardial viability ratio (SEVR) and carotid intima-media thickness (cIMT). Laboratory parameters, inflammation markers and lipid profile were also evaluated for all participants. There were no significant differences between patients and healthy individuals, as well as in our children population regarding PWV, SEVR, Aix and cIMT. However, significantly higher ESR, CRP and fibrinogen levels were detected in the total population of FMF patients and higher amyloid levels in FMF children, compared to controls. Atherogenic Index of Plasma was significantly higher both in the total patient population and in the subgroup of children, compared to controls. Furthermore, a significant positive correlation between Aix and CRP and a negative correlation between SEVR and ESR became apparent in the pediatric subgroup. Our study demonstrated no significant differences in vascular measurements between FMF patients and controls. The above could be attributed to the regular colchicine treatment, which seems to have a cardioprotective role against vascular damage.

Comparison of Valve Durability and Outcomes of Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Patients With Severe Symptomatic Aortic Stenosis and Less-Than-High-Risk for Surgery.

This study aimed to investigate the rate of severe structural valve deterioration (SVD) and long-term outcomes of patients with severe symptomatic aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). Propensity score matched analysis of patients who underwent TAVI (n = 216) and SAVR (n = 216) between 2008 and 2012. Long-term echocardiographic parameters and clinical outcomes were assessed after more than 6 years after TAVI/SAVR. Rate of severe SVD was 10.5% versus 4.5% in the TAVI and SAVR groups, respectively, but the difference was not statistically significant (hazard ratio [HR] 2.5; 95% confidence interval [CI] 0.7 to 8.3; p = 0.159). This was largely driven by higher rates of mean transprosthetic gradient ≥40 mm Hg (7.0 vs 3.4%; p = 0.327) and aortic regurgitation (4.7% vs 0%; p = 0.058). TAVI patients had lower survival rates at 6 years than SAVR patients (40.7% vs 59.6%, respectively, p <0.001, HR 2.15; 95% CI 1.45 to 3.20). Rate of cardiovascular events (14.4% TAVI vs 18.2% SAVR, HR 0.8; 95% CI 0.4 to 1.3; p = 0.347) and permanent pacemaker implantation (PPI; 16.0% TAVI vs 9.2% SAVR, p = 0.234) was similar between the 2 groups. In conclusion, incidence of moderate and severe SVD was not statistically different between TAVI and SAVR. Rate of moderate or severe aortic regurgitation was significantly higher in the TAVI group with predominant use of first-generation valves. Reintervention rate was low in both groups. Survival rate was lower after TAVI, probably because of higher frailty index, but incidence of cardiovascular events, PPI, and SVD was similar in both groups.

Pharmacological Management of Diabetic Nephropathy.

INTRODUCTION: Diabetes mellitus (DM) is one of the most common diseases worldwide. Its adverse effects on several body organs, have made treatment of DM a priority. One of the most serious complications of DM is diabetic nephropathy (DN). OBJECTIVE: The aim of this review is to critically discuss available data on the pharmacological management of DN. METHODS: A comprehensive review of the literature was performed to identify studies assessing the impact of several drug classes on DN. RESULTS: Several studies have been conducted in order to find a novel and effective treatment of DN. So far, the cornerstone therapy of DN consists of renin-angiotensin system (RAS) inhibitors, agents that decrease the synthesis of intrarenal angiotensin II or block its receptors. Their antiproteinuric and antihypertensive effects can not only decelerate the progress of DN but prevent its onset as well. Novel antidiabetic drugs, such as sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide- 1 receptor agonists (GLP-1 RA), are promising agents in the therapy of DN, due to their positive effect on renal and cardiovascular adverse events. From lipid-lowering agents, atorvastatin improves DN up to stage 3 and substantially reduces CVD. CONCLUSION: RAS inhibitors, SGLT-2i and GLP-1 agonists were found to be beneficial for the treatment of DN. Larger renal trials are needed in order to incorporate these drugs into the first line treatment of DN.

Juvenile Recurrent Parotitis: The Role of Sialendoscopy.

Juvenile recurrent parotitis (JRP) is a recurrent parotid inflammation of nonobstructive, nonsuppurative nature. It manifests in childhood and usually resolves after puberty but may also persist into adulthood. JRP is characterized by recurrent episodes of unilateral or/and bilateral parotid swelling with pain, reduction of salivary secretion, swallowing difficulty, fever, and malaise. The cause of this condition remains obscure. Throughout the last two decades, many therapeutic methods have been used in order to reduce the frequency and severity of JRP. During the acute episodes, conservative approaches (antibiotics, analgesics, sialogogues, massage of the parotid gland, and mouth rinses) are used. Parotidectomy has been suggested in rare selective occasions. Recently, a promising concept of sialendoscopy, which is a minimal invasive endoscopic technique, has been applied. This review outlines the literature on JRP focusing on methods and challenges in diagnosing JRP along with the differential diagnosis of JRP and the function of the parotid during JRP. In addition, we describe the treatment options for JRP, pointing out the importance of sialendoscopy as a diagnostic and treatment procedure that offers improvement in patients' daily life.

Drugs that Mimic the Effect of Gene Mutations for the Prevention or the Treatment of Atherosclerotic Disease: From PCSK9 Inhibition to ANGPTL3 Inactivation.

BACKGROUND: Drugs mimicking natural beneficial mutations, including that for familial hypercholesterolemia (FH), might represent the future of hypolipidemic drug treatment. OBJECTIVE: The aim of this review is to review the properties and the effects of these drugs, which are either already commercially available or are in the process to be approved for the treatment of dyslipidemia. RESULTS: More than a decade ago, it was accidentally discovered that proprotein convertase subtilisin/kexin type 9 (PCSK9) loss-of-function mutations resulted in marked lifelong reduction of LDL-C and the incidence of cardiovascular disease (CVD). This provided the idea for a human anti-PCSK9 antibody. Along with dozens of phase II and III studies demonstrating unprecedented reductions in LDL-C levels, two large clinical trials established the substantial benefits of evolocumab and alirocumab on cardiovascular morbidity and mortality, on top of standard treatment. Evolocumab and alirocumab are now approved and used in clinical practice for the treatment of FH, statin intolerance, and high risk patients not achieving LDL-C targets. Anti RNA, small molecules, peptides and also protein fragments against PCSK9 are in phase 1 trials. Angiopoietin-like protein 3 (ANGPTL3) regulates lipid metabolism increasing triglycerides (TGs), remnants, and LDL-C. In a huge study, ANGPTL3 deficiency due to gene(s) loss-of-function was associated with substantial reductions in circulating TGs, LDL-C, and CVD. Evinacumab, an ANGPTL3 antibody, caused a dose-dependent reduction in fasting TG levels of up to 76% and LDL-C of up to 23% and CVD risk by 41%. There is also antisense oligonucleotide and micro-RNA- 27b (miR-27b) against ANGPTL3. Two naturally occurring mutations in apo3 gene, A23T and K58E, reduce TGs and CVD risk. A monoclonal antibody targeting apoC-III has the same effect. CONCLUSION: Mimicking the beneficial naturally happening mutations in lipid metabolism pathways with biological drugs is probably the future of hypolipidemic drug treatment.

The Role of Mineralocorticoid Receptor Antagonists in Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Heart failure (HF) is a worldwide modern epidemic, associated with significant morbidity and mortality. Several causes have been identified for the syndrome, most of which share common pathophysiologic pathways, including neurohormonal activation. Central to the latter lies activation of the reninangiotensin- aldosterone system, and its effects on cardiovascular disease progression. OBJECTIVES: The aim of this review is to summarize the pathophysiology of aldosterone and the effects of its blockage in the failing heart, as well as to provide state-of-the-art evidence, and address future perspectives regarding the use of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction. METHOD: Literature was reviewed for studies that assess the pathophysiology of aldosterone in HF with reduced ejection fraction (HFrEF), and the effects of mineralocorticoid receptor antagonists (MRAs) in this condition. RESULTS: Several major society guidelines have synthesized the available evidence on HFrEF management, and drugs that block the renin-angiotensin-aldosterone system at different levels continue to form the key component of standard of care for these patients. Mineralocorticoid receptor antagonists are an important part of HFrEF pharmacologic treatment, and their use is supported by a high level of evidence studies. This class of drugs demonstrated significant benefits for morbidity and mortality, across the spectrum oh HFrEF, including patients after acute myocardial infarction. CONCLUSION: Current evidence supports the central role of aldosterone in HFrEF progression, and the significant benefits on outcomes with the use of MRAs.

Clinical Applications of Intravenous Immunoglobulins in Child Neurology.

BACKGROUND: While there are guidelines for the use of intravenous immunoglobulins in children with Guillain-Barre syndrome and myasthenia gravis based on high-level evidence studies, data are scarce for the majority of neurologic disorders in this age group. Neuronal antibodies are detected in children with seizures of autoimmune etiology. Intravenous immunoglobulins with their broad immunomodulatory mechanism of action could be ideally effective in different forms of immunedysregulated intractable epilepsies such as autoimmune epilepsy and autoimmune Rasmussen encephalitis. We conducted a systematic review of the literature for evidence of the use of intravenous immunoglobulins in a variety of neurologic diseases in childhood. METHOD: A comprehensive literature search was conducted using Pubmed as the medical database source without date range. Prospective studies in pediatric groups including objective measures of clinical outcomes were systematically selected. RESULTS: A total of 11 prospective studies were identified in the literature demonstrating a favorable effect of this therapeutic option in children with drug-resistant epilepsy and in cases of encephalitis. No serious adverse effects were reported. No prospective studies about the use of intravenous immunoglobulins in children with demyelinating disorders or neurologic paraneoplasmatic syndromes were found. CONCLUSION: In this review, we summarize the recent advances in the field of intravenous immunoglobulins used in pediatric neurological diseases. Literature data supports a beneficial effect in this age group. Whilst awaiting the results of large scale studies, administration of intravenous immunoglobulins could be justified in refractory child epilepsy. Otherwise, its use should be guided by the individual needs of each child, depending on the underlying neurological disease.