Corticosteroids in SARS-COV2 infection: certainties and uncertainties in clinical practice.

INTRODUCTION: The SARS-COV-2 pandemic is a worldwide public health problem due to the large medical burden and limited number of therapies available. Corticosteroids have a rather unclear efficacy in viral non-SARS-COV-2 pneumonias and therefore their use is not universally recommended. In SARS-COV-2 pneumonia however, it is expected that they can reduce the deleterious consequences of the virus-related systemic inflammation. AREAS COVERED: a MEDLINE search covering the period 1995-2020 was completed to identify relevant papers. SARS-COV-2 pathogenesis is very complex and is represented by the interplay of many cytokine-driven inflammation pathways. Its most severe form so called cytokine storm, is an exaggerate reaction of the host infected by the virus rapidly resulting in multiple organ dysfunction (MODS). Corticosteroids have the potential to blunt the inflammation response in such patients, but their efficacy is not the same for all patients. Further on the certainties and uncertainties regarding the efficacy of this therapy in SARS-COV-2 pneumonia are discussed. EXPERT OPINION: In patients with severe SARS-COV-2 pneumonia, corticosteroids can be efficacious, but it is still not clear if they can be safely used in patients with comorbid cardiovascular disease or how the optimal duration of therapy can be established.

Pharmacotherapy options in pulmonary alveolar proteinosis.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a heterogeneous group of rare diseases characterized by the abnormal production and impaired degradation of pulmonary surfactant as a result of malfunctioning of alveolar macrophages. This is due to the downstream dysregulation of the GM-CSF pathway, which can be caused by specific autoantibodies (autoimmune, aPAP formerly known as idiopathic iPAP), direct injury to alveolar macrophages (e.g. by toxic inhaled agents.), or by genetic defects (hereditary or congenital PAP). Few pharmacotherapy options are currently available to treat this disease. AREA COVERED: The authors discuss the exogenous administration of GM-CSF, rituximab, and the potential role of cholesterol lowering medications in this review. The authors, furthermore, provide their opinion on the available pharmacotherapeutic options and give their future perspectives. EXPERT OPINION: Inhaled GM-CSF remains the most commonly used therapy in patients with iPAP but other inhaled therapies such as PPARγ activators should be considered, especially in patients who are partially responsive or unresponsive to traditional treatments.

Roflumilast in patients with advanced chronic obstructive pulmonary disease: towards a better-targeted use.

INTRODUCTION: For patients with chronic obstructive pulmonary disease (COPD), one of the main goals in its management is to reduce the number of disease exacerbations. Roflumilast is an anti-inflammatory compound used in patients with advanced COPD and chronic bronchitis in order to fulfill this objective. However, this is not always easily achieved due to the heterogeneity of the population. Clinical trial data can allow more in-depth analysis in order to identify predictors for maximal efficacy in different patient populations. Areas covered: A post hoc pooled data analysis derived from two large-scale randomized controlled trials helped to better define the disease subsets in which roflumilast would exert the maximal therapeutic effect. These are represented by patients with prior hospitalizations for COPD exacerbations and by patients with higher values for eosinophil blood count. This analysis is the focus of our key paper evaluation. Expert opinion: This pooled data analysis suggests that a phenotype/endotype guided therapy has the potential to be impactful on overall survival by reducing the number of exacerbations and increase the life span of patients.

Belimumab and antipneumococcal vaccination in patients with systemic lupus erythematosus.

In systemic lupus erythematosus (SLE), flares can be caused by infections. In particular, Streptococcus pneumoniae infection can be severe or even potentially lethal in absence of previous immunization or in case of 'aggressive' systemic antibiotic therapy. Immunization efficacy, however, can be reduced in such patients with the use of the various immunosuppressive therapeutic regimens. In particular, the use of novel monoclonal antibodies against B lymphocytes raises concerns over the potential interference with antipneumococcal vaccination. Previous studies demonstrated that belimumab therapy did not significantly reduce the efficacy of antipneumococcal vaccination, when received after the initiation of belimumab therapy. The study being evaluated in this article investigated the efficacy of vaccination in relationship to initiation of belimumab therapy in SLE patients.

Triple fixed inhaled therapy in frequent chronic obstructive pulmonary disease exacerbators: potential advantages for various degrees of airways obstruction.

INTRODUCTION: Inhaled therapies are the therapeutic mainstay in stable chronic obstructive pulmonary disease (COPD). They are represented by long-acting bronchodilators (anticholinergics or beta2-agonists) and by inhaled corticosteroids, currently available as a monotherapy or as combination therapies in one inhaler. Combinations of anticholinergics and beta2 agonists or beta2 agonists and inhaled corticosteroids are widely used per the prescription guidelines. The advantage of them are related with higher adherence and better acceptability by the patients as compared to both components dosed with individual inhalers. Bronchodilator combinations have also been demonstrated to exhibit a superior efficacy due to their synergistic mechanism of action when compared to either monotherapy. Triple therapies with anticholinergic-beta2 agonist-inhaled corticosteroid have been under investigation over the last few years and recently one such product became available in the EU for the treatment of stable COPD. Areas covered: The the FULFIL trial (Lung FUnction and quality of LiFe assessment in COPD with closed trIpLe therapy) investigated the efficacy and safety of fluticasone/vilanterol/umeclidinium once daily therapy in COPD patients. Expert opinion: The results discussed in this paper support the use of this combination in advanced COPD but also in earlier stages in patients with frequent exacerbation. However further and more long-term assessments are required.

Clinical education and training of student nurses in four moderately new European Union countries: Assessment of students' satisfaction with the learning environment.

Nurses underwent different models of education during various historical periods. The recent decade in Europe has been marked with educational transitions for the nursing profession related to Bologna Declaration and enlargement of the European Union. This paper aims to explore the situation of clinical placements for student nurses and assess students' satisfaction with the learning environment in four relatively new member states of European Union: the Czech Republic, Hungary, Lithuania and Romania. The data for cross-sectional quantitative study were collected during the exploratory phase of EmpNURS Project via a web based questionnaire which utilized a part of Clinical Learning Environment scale (CLES + T). The students evaluated their clinical learning environment mainly positively. The students' utter satisfaction with their clinical placements reached a high level and strongly correlated with the supervisory model. Although the commonest model for supervision was traditional group supervision, the most satisfied students had the experience of individualised supervision. The study gives a picture of the satisfaction of students with the learning environment and, moreover, with clinical placement education of student nurses in four EU countries. The results highlight the individualized supervision model as a crucial factor of students' total satisfaction during their clinical training periods.

Nivolumab for advanced non-small cell lung cancer: an evaluation of a phase III study.

Lung cancer still remains associated with a high mortality rate and more efficacious therapies are needed in order to improve the disease outcome. Nivolumab is a monoclonal antibody which blocks the programmed death-1 receptor which is currently evaluated in phase III clinical trials in advanced lung cancer. Here, we evaluate the results of a phase III study in which nivolumab efficacy and safety were compared to those of docetaxel. Nivolumab was able to improve survival and progression-free survival and exhibited a very good safety profile. Further clinical data are needed in order to better position this therapy among the existing methods. The promising results support the use of this therapy as a stand-alone approach.

Evaluation of inhaled tiotropium in asthma, uncontrolled with standard combination therapy.

INTRODUCTION: In uncontrolled asthma, the suboptimally inhibited airways inflammation is the main pathogenic event. Addition of other medications to the regular regimen might be able to improve disease control by enhancing bronchodilation and/or by reducing the bronchial inflammation. Tiotropium is currently under evaluation as a potential such therapy. AREAS COVERED: The long-term efficacy and safety of tiotropium was recently evaluated in two studies in patients with poorly controlled asthma under inhaled corticosteroids + long-acting ß2 agonists. Tiotropium was able to improve lung function and the effect was sustained, reduced the exacerbations risk (and in particular severe exacerbations risk), but had a marginal effect on symptoms and on quality of life. EXPERT OPINION: In asthma, inhaled tiotropium is able to increase the bronchodilation, and might also be able to exert an anti-inflammatory effect.

Tralokinumab for uncontrolled asthma.

INTRODUCTION: Asthma is a chronic inflammatory disease of the airways mainly related to allergen exposure, in which various cytokine-specific pathways interact among themselves to promote IgE hyperproduction, bronchial hyperresponsiveness, eosinophil local recruitment and airways remodeling. IL-13 is known for its prominent pathogenic role in this disease and therapeutic blocking approaches are underway. AREAS COVERED: Anti-IL-13 antibodies are currently investigated in clinical studies in uncontrolled asthma. Tralokinumab is a human IgG4 anti IL-13 antibody which was recently evaluated in a Phase II study demonstrating the maximal efficacy in a subset of asthma patients characterized by the highest sputum IL-13 levels. The results of this study are discussed in this paper. EXPERT OPINION: The IL-13 blockade with various therapeutic approaches such as tralokinumab has the potential to improve the asthma control in patients subsets in whom the blocked cytokine is demonstrated to be overexpressed.

[Refractory arterial hypertension]. / Hipertensiunea arteriala rezistenta la tratament.

The present review synthesizes "the state of the art" concerning resistant (refractory) arterial hypertension (RAH). Definition, epidemiology, frequent risk factors, clinical conditions and causes of therapeutic resistance of RAH are revisited. Pathogenic hypothesis and related therapeutic approaches are explored. The paper lists current and new pharmacological therapies of RAH and introduces the latest interventional approach (the Rheos BHT system) to this form of arterial hypertension.

[Peripartum cardiomyopathy]. / Cardiomiopatia peripartum.

Peripartum cardiomyopathy (CMP) represents an intriguing and incompletely characterised cause of heart failure arising in women without previously known heart disease during last trimester of pregnancy or first 20 weeks after birth. Fundamental clinical and basic research is lacking regarding this rare but potentially devastating disorder. The article reviews present accepted definition of CMP, epidemiological data, possible etiologic factors and pathogenic mechanisms proposed in CMP. It describes identified risk factors for CMP, clinical symptoms and signs, diagnostic assessment and treatment. Prognosis, follow up criteria and education for patients with previous CMP concerning subsequent pregnancies are also described.