Atherothrombosis and Oxidative Stress: Mechanisms and Management in Elderly

Significance: The incidence of cardiovascular events (CVEs) increases with age, representing the main cause of death in an elderly population. Aging is associated with overproduction of reactive oxygen species (ROS), which may affect clotting and platelet activation, and impair endothelial function, thus predisposing elderly patients to thrombotic complications. Recent Advances: There is increasing evidence to suggest that aging is associated with an imbalance between oxidative stress and antioxidant status. Thus, upregulation of ROS-producing enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase, along with downregulation of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, occurs during aging. This imbalance may predispose to thrombosis by enhancing platelet and clotting activation and eliciting endothelial dysfunction. Recently, gut-derived products, such as trimethylamine N-oxide (TMAO) and lipopolysaccharide, are emerging as novel atherosclerotic risk factors, and gut microbiota composition has been shown to change by aging, and may concur with the increased cardiovascular risk in the elderly. Critical Issues: Antioxidant treatment is ineffective in patients at risk or with cardiovascular disease. Further, anti-thrombotic treatment seems to work less in the elderly population. Future Directions: Interventional trials with antioxidants targeting enzymes implicated in aging-related atherothrombosis are warranted to explore whether modulation of redox status is effective in lowering CVEs in the elderly

Hypercoagulation and antithrombotic treatment in coronavirus 2019. a new challenge

The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number of patients needing mechanical ventilation or intensive care units treatment and for the elevated mortality risk. A link between COVID-19 and multiorgan failure may be dependent on the fact that most COVID-19 patients are complicated by pneumonia, which is known to be associated with early changes of clotting and platelet activation and artery dysfunction; these changes may implicate in thrombotic-related events such as myocardial infarction and ischemic stroke. Recent data showed that myocardial injury compatible with coronary ischemia may be detectable in SARS-CoV-2 patients and laboratory data exploring clotting system suggest the presence of a hypercoagulation state. Thus, we performed a systematic review of COVID-19 literature reporting measures of clotting activation to assess if changes are detectable in this setting and their relationship with clinical severity. Furthermore, we discussed the biologic plausibility of the thrombotic risk in SARS-CoV-2 and the potential use of an antithrombotic treatment

The EPP server of the .it Registry: main features and functionalities

This document outlines a method for the various registries for implementing their EPP client so that it interacts correctly with the synchronous server of the Italian registry. There are three categories of such EPP commands. Commands for: - managing sessions (login, logout, hello) - querying the server without modifying the status of the Contact and Domain objects - for modifying the status of the Contact and Domain objects For each command you will see an example of a request and how the server responds. There are also some examples of responses to errors for cases where the EPP command has not been correctly submitted or submitted in a status in which the command itself is not permitted

Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects

Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet and seems to account for the protective effect against cardiovascular disease. However, the underlying mechanism is still elusive

Malocclusion and rhinitis in children: an easy-going relationship or a yet to be resolved paradox? A systematic literature revision

Objective: The relation between nasal flow and malocclusion represents a practical concern to pediatricians, otorhinolaryngologists, orthodontists, allergists and speech therapists. If naso-respiratory function may influence craniofacial growth is still debated. Chronic mouth-breathing is reported to be associated also with a characteristic pattern of dental occlusion. On the other hand, also malocclusion may reduce nasal air flows promoting nasal obstruction. Hereby, the aim of this review was to describe the relationship between rhinitis and malocclusion in children. Methods: An electronic search was conducted using online database including Pubmed, Web of Science, Google Scholar and Embase. All studies published through to January 30, 2017 investigating the prevalence of malocclusion in children and adolescents (aged 0-20 years) affected by rhinitis and the prevalence of rhinitis in children with malocclusion were included. The protocol was registered at PROSPERO - International prospective register of systematic reviews under CRD42016053619. Results: Ten studies with 2733 patients were included in the analysis. The prevalence of malocclusion in children with rhinitis was specified in four of the studies ranging from as high as 78.2% to as low as 3%. Two out of the studies reported the prevalence of rhinitis in children with malocclusion with a rate ranging from 59.2 to 76.4%. Conclusion: The results of this review underline the importance of the diagnosis and treatment of the nasal obstruction at an early age to prevent an altered facial growth, but the data currently available on this topic do not allow to establish a possible causal relationship between rhinitis and malocclusion

Imbalance between nitric oxide generation and oxidative stress in patients with peripheral arterial disease: Effect of an antioxidant treatment

BackgroundNitric oxide (NO), a potent vasodilator produced by endothelial cells, is reduced in patients with peripheral arterial disease (PAD), but the mechanism has not been fully elucidated. Because NO is rapidly inactivated by superoxide anion, we speculated that enhanced oxidative stress could lower NO generation. The aim of our study was to investigate if an imbalance between oxidative stress and NO does exist in patients with PAD and if an increase of NO formation could be achieved by an antioxidant treatment.MethodsIn a first study, serum levels of nitrite and nitrate (NOx), markers of NO generation, and 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress and maximal walking distance (MWD), were measured in 40 PAD patients and 40 controls. In a second study, 10 PAD patients were randomly allocated in a crossover design to intravenous propionyl-L-carnitine (6 g/day) or placebo for 7 days, with a washout of 30 days between the two phases of the trial. Serum levels of NOx and 8-OHdG were measured before and after the study.ResultsCompared with controls, serum levels of 8-OHdG (mean ± SD) were significantly increased in PAD patients (4.4 ± 3.1 ng/mL vs 2.4 ± 1.2 ng/mL; P < .001), and serum levels of NOx were significantly decreased (11.6 ± 6 μM vs 17 ± 6.1 μM; P < .001). Levels of 8-OHdG and NOx were inversely correlated (r = −0.879; P < .001). Serum levels 8-OHdG were inversely correlated with MWD (r = −0.48, P = .002). The interventional trial showed no changes in the patients given placebo. Patients treated with propionyl-L-carnitine showed a significant increase of MWD from 101 ± 31 meters to 129 ± 35 meters (P = .007) and in NOx from 14.5 ± 4.5 μM to 17.1 ± 3.8 μM (P = .007). A significant decrease of 8-OHdG from 3.6 ± 1.1 ng/mL to 2.6 ± 1 ng/mL was also found (P = .005.)ConclusionsThis study suggests that in PAD patients, the reduction of NO generation could be dependent upon enhanced oxidative stress

Soluble CD40 ligand predicts ischemic stroke and myocardial infarction in patients with nonvalvular atrial fibrillation

OBJECTIVE - Atrial fibrillation (AF) is associated with a high incidence of vascular disease that may be related to a prothrombotic and inflammatory state. Soluble CD40 ligand (sCD40L), which stems essentially from platelet activation, possesses inflammatory and prothrombotic properties. The aim of the study was to assess whether sCD40L is a predictor of stroke or myocardial infarction (MI) in patients with nonvalvular AF. METHODS AND RESULTS - Plasma levels of sCD40L were measured in 231 patients (177 [77%] had permanent or persistent AF, and 54 [23%] had paroxysmal AF). Patients were followed for a mean period of 27.8±8.8 months, and cardiovascular events such as fatal and nonfatal stroke and MI were recorded. AF population was divided in 2 groups according to sCD40L level above or below the median (4.76 ng/mL). The 2 patients' groups had similar distribution of cardiovascular risk factors, age, gender, medications, or serum C-reactive protein levels. During the follow-up period, vascular events occurred in 6 (2 nonfatal MI and 4 nonfatal ischemic strokes) of 116 patients with low levels of sCD40L (5.1%) and in 29 (11 fatal and 3 nonfatal MI; 3 fatal and 12 nonfatal ischemic strokes) of 115 patients with high levels (25.2%) (log-rank test: P<0.001). Using the COX proportional Hazards model, patients with sCD40L above the median were 4.63 times more likely to experience a vascular event (95% C.I.: 1.92 to 11.20). CONCLUSIONS - This study shows that enhanced soluble CD40L level is a predictor of vascular events in patients with nonvalvular AF, thus suggesting that enhanced platelet activation may play a role in its clinical progression. © 2007 American Heart Association, Inc

Effects of repeated intravitreal injections of dexamethasone implants on intraocular pressure: a 4-year study

Purpose: Dexamethasone and other corticosteroids are administered intravitreally to treat a variety of retinal diseases. As a side effect, they can alter intraocular pressure (IOP). The purpose of this study is to describe the incidence, severity, and management of ocular hypertension following the administration of multiple intravitreal injections of dexamethasone implants. Materials and Methods: A total of 78 eyes of 78 subjects (males 62%; females 38%; mean age 67 ± 13 years SD) received a total of 152 intravitreal injections of 0.7 mg dexamethasone implants over 4 years. Indications included retinal vein occlusion (87%), diabetic macular edema (9%), wet-type age-related macular degeneration (4%). Ocular hypertension was defined as intraocular pressure above 23 mmHg or any pressure increase of 10 mmHg or more from baseline values. IOP was measured by applanation tonometry before the injection (T0), as well as one week (T1), one month (T2), and three months (T3) afterwards. Results: Five percent (4/78) of subjects developed ocular hypertension after the 1st injection. On the second and third rounds, additional 7.2% (3/42) and 4.2% (1/24) of subjects developed the same side effect. Among the 8 subjects who received a fourth injection, none was found with OHT. Pressure elevations were detected at T2 and T3. In all patients, topical medical therapy was sufficient to lower the IOP below threshold. Mean pressure variations following the first injection as compared to previous recorded values were +0.97 mmHg (T1), +0.92 mmHg (T2), and −0.41 mmHg (T3) (p &lt; 0.05). Mean pressure variations following the second injection were +0.54 mmHg (T1), +0.23 mmHg (T2) and −0.66 mmHg (T3) (p &lt; 0.05). Conclusion: Ocular hypertension is a recognized side effect of intravitreal dexamethasone. Some patients develop it right after the first injection, while others develop it subsequently, on the 2nd or 3rd round. This side effect becomes most apparent 30–90 days following the implantation procedure and responds well to topical pressure-lowering medications