Discovery of a Novel Inhaled PI3Kδ Inhibitor for the Treatment of Respiratory Diseases.

Oral PI3Kδ inhibitors such as Idelalisib and Duvelisib have shown efficacy as anticancer agents and Idelalisib has been approved for the treatment of three B-cell cancers. However, Idelalisib has a black box warning on its product label regarding the risks of fatal and serious toxicities including hepatic toxicity, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation. Some of these side effects are mechanism-related and could hinder the development of Idelalisib for less severe conditions.

Discovery of a Potent, Selective, and Orally Available PI3Kδ Inhibitor for the Treatment of Inflammatory Diseases.

The delta isoform of the phosphatidylinositol 3-kinase (PI3Kδ) has been shown to have an essential role in specific immune cell functions and thus represents a potential therapeutic target for autoimmune and inflammatory diseases. Herein, the optimization of a series of pyrrolotriazinones as potent and selective PI3Kδ inhibitors is described. The main challenge of the optimization process was to identify an orally available compound with a good pharmacokinetic profile in preclinical species that predicted a suitable dosing regimen in humans.

[Epidemiological profile and sensitivity pattern of isolates causing invasive fungal infection vs. colonizing isolates in non-neutropenic critically ill patients].

Background: Patients admitted to critical care units can be infected with a large number of fungal isolates that are occasionally responsible for invasive fungal infections (IFI).

Aims: To describe the epidemiological profile and antifungal susceptibility patterns of fungal isolates in our unit, and to identify key risk factors associated with the development of IFI.

Methods: A descriptive cohort and retrospective study with patients admitted to a polyvalent Critical Care Unit of a university hospital was carried out.

Sirolimus-Eluting Stents vs Uncoated Stents for the Treatment of Proximal Left Anterior Descending Coronary Artery Stenosis.

Sirolimus-eluting stents (SES) have demonstrated low incidence of target vessel revascularizations in several anatomic scenarios, including proximal left anterior descending coronary artery (pLAD) lesions. The aim of present study was to compare the efficacy of SES with bare metal stents (BMS) for the treatment of such lesions. 96 patients with severe pLAD stenosis treated with SES were included.

Two-year follow-up of sirolimus-eluting stents for the treatment of proximal left anterior descending coronary artery stenosis.

Introduction: Sirolimus-eluting stents (SES) have demonstrated low target vessel revascularizations and low incidence of angiographic restenosis in several clinical scenarios. The aim of the present study was to assess the efficacy and safety of SES for the treatment of proximal left anterior descending coronary artery (pLAD) lesions.

Methods: Ninety-six patients with severe pLAD stenosis were enrolled.

Are there ethnic differences in the circadian variation in onset of acute myocardial infarction? A comparison of 3 ethnic groups in Birmingham, UK and Alicante, Spain.

We hypothesised that ethnicity may influence the circadian pattern in acute myocardial infarction (MI), in view of the potential differences in genetic background, cardiovascular risk factors and cultural habits. To test our hypothesis, we studied 340 consecutive acute MI patients (268 males; mean age 61.6+/-12.

A pharmacogenetic effect of factor XIII valine 34 leucine polymorphism on fibrinolytic therapy for acute myocardial infarction.

Objectives: The aim of this study was to evaluate the pharmacogenetic role of the factor XIII (FXIII) valine 34 leucine (Val34Leu) polymorphism in the fibrinolytic therapy of acute myocardial infarction (MI).

Background: Fibrinolytic therapy is an established treatment for acute MI, but up to 40% of treated patients do not achieve optimal tissue reperfusion. The FXIII Val34Leu polymorphism is one of the most relevant functional polymorphisms described in the haemostatic system.