Intravenous colistimethate administration and colistin lung tissue concentrations

n/

Upregulation of Myxovirus-resistance Protein A: A Possible Marker of Type I Interferon Induction in Systemic Sclerosis

ObjectiveTo examine whether myxovirus-resistance protein A (MxA) mRNA expression, commonly considered a reliable marker of Type I interferon (IFN) bioactivity, is modified in patients with systemic sclerosis (SSc); if it is associated to specific clinical features; and if its modulation is accompanied by modulation of mRNA for the Type I IFN receptor (IFNAR).MethodsQuantification of mRNA for MxA and the subunit IFNAR1 and isoforms of IFNAR2 was performed by real-time polymerase chain reaction in 50 patients with SSc. Results were compared with those obtained from healthy controls and patients with another autoimmune disease such as multiple sclerosis.ResultsLevels of MxA mRNA above the 99th percentile of values found in healthy controls were observed in 9 out of 50 patients with SSc (p < 0.001). Induced MxA expression was significantly associated with some features of more severe disease, such as lower forced vital capacity and the presence of ischemic digital ulcers. No differences in the levels of IFNAR were found within MxA-induced and MxA-non-induced patients, but there was a direct correlation between levels of MxA and the soluble isoform of IFNAR2.ConclusionOur results show induction of MxA expression in some patients with SSc, which correlates with the presence of ischemic ulcers and other signs of worse disease, suggesting a potential role of Type I IFN in the pathogenesis of this disease and/or its complications

Drug management of atrial fibrillation in light of guidelines and current evidence: an Italian Survey on behalf of Italian Association of Arrhythmology and Cardiac Pacing

AimAtrial fibrillation is a multifaceted disease requiring personalized treatment, in accordance with current ESC guidelines. Despite a wide range of literature, we still have various aspects dividing the opinion of the experts in rate control, rhythm control and thromboembolic prophylaxis. The aim of this survey was to provide a country-wide picture of current practice regarding atrial fibrillation pharmacological management according to a patient's characteristics.MethodsData were collected using an in-person survey that was administered to members of the Italian Association of Arrhythmology and Cardiac Pacing.ResultsWe collected data from 106 physicians, working in 72 Italian hospitals from 15 of 21 regions. Our work evidenced a high inhomogeneity in atrial fibrillation management regarding rhythm control, rate control and thromboembolic prophylaxis in both acute and chronic patients. This element was more pronounced in settings in which literature shows a lack of evidence and, consequently, the indications provided by the guidelines are weak or absent.ConclusionThis National survey evidenced a high inhomogeneity in current approaches adopted for atrial fibrillation management by a sample of Italian cardiologist experts in arrhythmia management. Further studies are needed to explore if these divergences are associated with different long-term outcomes

Direct oral anticoagulants for secondary prevention in patients with non-valvular atrial fibrillation

The patients with non-valvular atrial fibrillation (NVAF), both permanent and paroxysmal, and history of previous transient ischemic attack (TIA) or stroke represent a category of patients at high risk of new embolic events, independently of the presence of other risk factors. In these patients, national and international guidelines recommend oral anticoagulants as first choice for antithrombotic prevention. Direct oral anticoagulants (DOACs) have been demonstrated to be not inferior to warfarin for many end points in NVAF patients in terms of efficacy and safety. The post hoc analysis in selected subgroups of patients enrolled in the three mega trials of phase III comparing DOACs (RE-LY, ROCKET-AF and ARISTOTLE) with warfarin help to evaluate whether superiority and non-inferiority persist in these subgroups. Here, patients with NVAF and history of previous TIA/stroke receiving DOACs as secondary prevention are compared with patients with the same characteristics receiving warfarin. An analysis of these patients has been recently published (separately for each of three DOACs). This analysis shows that DOACs maintain their non-inferiority when compared with warfarin in secondary prevention, representing a real alternative in this context of patients at high risk for ischemic and bleeding events

efficacia e sicurezza dei nuovi farmaci anticoagulanti orali rispetto al warfarin nella profilassi cardioembolica del paziente con fibrillazione atriale non valvolare piu luci che ombre

Summary Introduction The prophylaxis of thromboembolic events represents a key point in the modern management of patients with non valvular atrial fibrillation (AF), both paroxysmal and persistent/permanent. Up to now, vitamin K antagonist (VKA) drugs are the first choice in thromboembolic prophylaxis. Their treatment limitations have lead to development and clinical experimental use of new molecules aimed to overcome their limits. The new oral anticoagulants, such as dabigatran, a direct inhibitor of thrombin or rivaroxaban and apixaban, direct inhibitors of activated factor X, have been compared to warfarin in randomized clinical phase three trials (RCTs) for thromboembolic prevention in patients with non valvular AF with the aim to demonstrate their non inferiority when compared to warfarin. The results of these trials have been recently published. In this article the authors review the results of efficacy and safety of these three more recently published large RCTs. Conclusions All RCTs, RE-LY for dabigatran, ROCKET-AF for rivaroxaban and ARISTOTLE for apixaban met the study end-points and demonstrated a good safety profile of each new oral anticoagulant, so promising a new era for thromboembolic prevention therapy in AF

Incidence and Predictors of Infections and All-Cause Death in Patients with Cardiac Implantable Electronic Devices: The Italian Nationwide RI-AIAC Registry

The incidence of infections associated with cardiac implantable electronic devices (CIEDs) and patient outcomes are not fully known. To provide a contemporary assessment of the risk of CIEDs infection and associated clinical outcomes. In Italy, 18 centres enrolled all consecutive patients undergoing a CIED procedure and entered a 12-months follow-up. CIED infections, as well as a composite clinical event of infection or all-cause death were recorded. A total of 2675 patients (64.3% male, age 78 (70-84)) were enrolled. During follow up 28 (1.1%) CIED infections and 132 (5%) deaths, with 152 (5.7%) composite clinical events were observed. At a multivariate analysis, the type of procedure (revision/upgrading/reimplantation) (OR: 4.08, 95% CI: 1.38-12.08) and diabetes (OR: 2.22, 95% CI: 1.02-4.84) were found as main clinical factors associated to CIED infection. Both the PADIT score and the RI-AIAC Infection score were significantly associated with CIED infections, with the RI-AIAC infection score showing the strongest association (OR: 2.38, 95% CI: 1.60-3.55 for each point), with a c-index = 0.64 (0.52-0.75), p = 0.015. Regarding the occurrence of composite clinical events, the Kolek score, the Shariff score and the RI-AIAC Event score all predicted the outcome, with an AUC for the RI-AIAC Event score equal to 0.67 (0.63-0.71) p < 0.001. In this Italian nationwide cohort of patients, while the incidence of CIED infections was substantially low, the rate of the composite clinical outcome of infection or all-cause death was quite high and associated with several clinical factors depicting a more impaired clinical status

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores &gt;2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores &gt;2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score &gt;2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores &gt;2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores &gt;2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Oxidative stress in applied basic research and clinical practice - Studies on experimental models

A simple, up to date search in PubMed gets over 90000 results for "oxidative stress". The interest on oxidative stress in the field of basic and medical research is remarkable (Parkinson's disease, G6PDH deficiency, or diabetes are only a few examples). "Studies on experimental models", published by Humana Press, pertaining to the series "Oxidative Stress in Applied Basic Research and Clinical Practice", is a tool for the study and reflections on oxidative stress and its implications for clinical research....