Conditional ligands for Asian HLA variants facilitate the definition of CD8+ T‐cell responses in acute and chronic viral diseases

Conditional ligands have enabled the high‐throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation‐sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA‐A, ‐B, and ‐C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA‐based MHC stability assay. HLA tetramers with redirected specificity could detect antigen‐specific CD8⁺ T‐cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein‐Barr virus (EBV) infections. The potential of this population‐centric HLA library was demonstrated with the characterization of seven novel T‐cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state‐of‐the‐art epitope prediction. This flow cytometry‐based technology therefore holds considerable promise for monitoring clinically relevant antigen‐specific T‐cell responses in populations of distinct ethnicity.     

Ventilation/perfusion (V/Q) scanning in contemporary patients with pulmonary embolism: utilization rates and predictors of use in a multinational study

Journal of Thrombosis and Thrombolysis - Ventilation/perfusion (V/Q) imaging and computed tomography pulmonary angiography (CTPA) are common tools for acute pulmonary embolism (PE) diagnosis....     

Favourable effects of heart rate reduction with intravenous administration of ivabradine in patients with advanced heart failure

BACKGROUND: Heart rate (HR) reduction may be useful in treatment of patients with heart failure (HF). There are no data on the haemodynamic effects of ivabradine (a selective I(f) current inhibitor) in advanced HF patients. AIMS: To assess the haemodynamic effects of ivabradine in patients with advanced HF and markedly depressed left ventricular (LV) function. METHODS AND RESULTS: Ten NYHA class III patients (50+/-12 years, LV ejection fraction 21+/-7%) underwent 24-h haemodynamic monitoring. Ivabradine 0.1 mg/kg was infused over 90', followed by 0.05-0.075 mg/kg in the subsequent 90'. Baseline HR was 93+/-8 bpm, cardiac index (CI) 2.2+/-0.6 l/min*m2; LV stroke volume 44+/-11 ml and systolic work 39+/-13 g. Ivabradine significantly reduced HR, by a maximum of 27% (to 68+/-9 bpm) at 4 h, without decreasing CI. Ivabradine increased stroke volume and LV systolic work by a maximum of 51% (to 66+/-17 ml) and 53% (to 58+/-20 g) at 4 h. No serious adverse events occurred. CONCLUSION: In patients with advanced HF and markedly depressed LV function, the acute administration of ivabradine is well tolerated, effectively reduces HR, markedly increases stroke volume and preserves cardiac output. Ivabradine appears a promising approach for the treatment of patients with moderate and advanced heart failure.     

The immune tolerant phase of chronic HBV infection: new perspectives on an old concept

Chronic hepatitis B virus (HBV) infection progresses through distinct disease phases that are strongly associated with patient age. The so-called immune tolerant (IT) phase represents the classical early phase of infection; it is associated with high levels of HBV replication and lack of clinical signs of liver Inflammation. Whether this phase of HBV infection is also associated with immunological features of “tolerance'' has recently been challenged. Here, we review the data that dispute this concept of immune tolerance and then propose an alternative interpretation of the immunopathological events that take place during this early phase of CHB infection.     

Quality of Life and Congenital Heart Disease in Childhood and Adolescence

Advances in cardiac surgery techniques and early diagnosis have enabled the increased survival of individuals with congenital heart disease. The investigation of the quality of life in children and adolescents with congenital heart disease provides complementary information to clinical data that can assist in decision making on the part of health professionals. Although many studies have been conducted to investigate the quality of life of children and adolescents with congenital heart disease, the results prove to be contradictory; while some studies show that congenital heart disease can impact the quality of life, others describe a better perception of quality of life among children and adolescents who suffer from the disease when compared with healthy control subjects. The purpose of this study is to review the literature on the assessment of health related quality of life in children and adolescents with congenital heart disease, in order to systematize the existing knowledge on this topic today. It is observed that research seeks to investigate aspects of personality in cardiac patients, their coping strategies used and perceived social support, aiming at better understanding the association of these variables with the level of quality of life in this population.     

Paclitaxel coated balloons for coronary artery interventions: A comprehensive review of preclinical and clinical data

After the "mechanical era" in interventional cardiology (represented by balloon angioplasty and bare metal stent implantation), arrived the "local dispensing" era, began with the intracoronary delivery of antithrombotic or antirestenotic drugs. However, even drug eluting stents have some pitfalls and cannot be used in all clinical subsets. In this article we will review the significant data on the paclitaxel-coated balloons for the treatment of coronary artery disease. Particularly, we will review the rationale of this new treatment strategy, the preclinical data and will focus on available clinical studies in humans. After the initial boost of the paclitaxel coated balloons with the Paccocath technology in in-stent restenotic lesions, the experimentation of newer devices in native coronary arteries raised some concerns on their efficacy and safety. We will comment on this topic trying to understand the reasons of this failure, and will discuss on possible future developments and applications for these devices for the treatment of coronary artery disease.