Clinical trial design, end-points, and emerging therapies in pulmonary arterial hypertension.

Clinical trials in pulmonary arterial hypertension (PAH) have led to the approval of several effective treatments that improve symptoms, exercise capacity and clinical outcomes. In phase 3 clinical trials, primary end-points must reflect how a patient "feels, functions or survives". In a rare disease like PAH, with an ever-growing number of treatment options and numerous candidate therapies being studied, future clinical trials are now faced with challenges related to sample size requirements, efficiency and demonstration of incremental benefit on traditional end-points in patients receiving background therapy with multiple drugs.

Lung Cancer and Interstitial Lung Diseases.

Lung cancer continues to be one of the leading causes of cancer-related death worldwide. There is evidence of a complex interplay between lung cancer and interstitial lung disease (ILD), affecting disease progression, management strategies, and patient outcomes. Both conditions develop as the result of common risk factors such as smoking, environmental exposures, and genetic predispositions.

Transcriptional profiling unveils molecular subgroups of adaptive and maladaptive right ventricular remodeling in pulmonary hypertension.

Right ventricular (RV) function is critical to prognosis in all forms of pulmonary hypertension. Here we perform molecular phenotyping of RV remodeling by transcriptome analysis of RV tissue obtained from 40 individuals, and two animal models of RV dysfunction of both sexes. Our unsupervised clustering analysis identified 'early' and 'late' subgroups within compensated and decompensated states, characterized by the expression of distinct signaling pathways, while fatty acid metabolism and estrogen response appeared to underlie sex-specific differences in RV adaptation.

A common gene signature of the right ventricle in failing rat and human hearts.

The molecular mechanisms of progressive right heart failure are incompletely understood. In this study, we systematically examined transcriptomic changes occurring over months in isolated cardiomyocytes or whole heart tissues from failing right and left ventricles in rat models of pulmonary artery banding (PAB) or aortic banding (AOB). Detailed bioinformatics analyses resulted in the identification of gene signature, protein and transcription factor networks specific to ventricles and compensated or decompensated disease states.

Impact of COVID-19 infection on lung function and nutritional status amongst individuals with cystic fibrosis: A global cohort study.

Background: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF).

Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021.

Association of Phosphodiesterase-5 Inhibitor Treatment With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry.

Background: Patients with COPD frequently demonstrate pulmonary hypertension (PH). Severe PH in patients with COPD, identified by pulmonary vascular resistance (PVR) of > 5 Wood units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear.

Data Integration for a Global Deep-Phenotyping Registry for Pulmonary Hypertension - Lessons Learned.

The integration of data from various healthcare centers into disease registries is pivotal for facilitating collaborative research and enhancing clinical insights. In this study, we investigate the integration process of existing registries into the PVRI GoDeep meta-registry, focusing on the complexities and challenges encountered. We detail the integration process, including data transformation, mapping updates, and feedback mechanisms.

Pretransplant NT-proBNP levels are associated with mortality among lung transplant recipients.

The prognostic significance of pretransplant N-terminal pro-brain (B)-type natriuretic peptide (NT-proBNP) level has not been investigated in lung transplant recipients. The electronic files of 173 patients with chronic lung disease who underwent lung transplantation in 2018-2022 at a tertiary medical center were retrospectively reviewed. Right heart catheterization (RHC) and NT-proBNP determination were performed preoperatively in all cases.

Bitter tastants relax the mouse gallbladder smooth muscle independent of signaling through tuft cells and bitter taste receptors.

Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder.

Evaluation of a medical student-delivered smoking prevention program utilizing a face-aging mobile app for secondary schools in Germany: The Education Against Tobacco cluster-randomized controlled trial.

Background: To reduce smoking uptake in adolescents, the medical students' network Education Against Tobacco (EAT) has developed a school-based intervention involving a face-aging mobile app (Smokerface).

Methods: A two-arm cluster-randomized controlled trial was conducted, evaluating the 2016 EAT intervention, which employed the mobile app Smokerface and which was delivered by medical students. Schools were randomized to intervention or control group.

Reversed halo sign as a radiological feature of tuberculosis - Report of two cases.

Reversed halo sign (RHS) is a radiological feature described as a focal, rounded area of ground-glass opacity surrounded by a ring of consolidation. In this report we describe two unique radiological cases demonstrating diffuse bilateral infiltrates with multiple RHSs in chest CT scans. Both patients were ultimately diagnosed as having tuberculosis (TB) and had been exposed to silica in the past.

Air travel in patients suffering from pulmonary hypertension-A prospective, multicentre study.

The PEGASUS study is the first multicentric and prospective assessment of the safety of air travel flying in pulmonary hypertension (PH) (NCT03051763). Data of air travel from 60 patients with PH was available. No severe adverse events occurred.

Adenomatous hyperplasia induced by chronic cherry pit retention mimicking an endobronchial tumor-case series and systematic review of literature.

Introduction: Endobronchial foreign body aspiration is not common in adults, but it is a life-threatening event. Recurrent pneumonias by chronic retention of foreign body often lead to initial medical presentation of the patient. However, lymphoplasmacellular bronchitis with adenomatous hyperplasia and squamous epithelium metaplasia with complete or partial blockage of lobar bronchus mimicking lung tumor is rare in literature, and this particular condition is often misdiagnosed.

High antinuclear antibody titer is associated with increased mortality risk in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a diagnosis of exclusion, requiring that potential etiologies of interstitial lung disease be ruled out. Antinuclear antibody (ANA) testing is commonly performed in individuals with IPF, but the clinical significance of ANA positivity remains uncertain. A retrospective search identified 161 patients diagnosed with IPF between May 2010 and January 2021.

A safety evaluation of intermittent high-dose inhaled nitric oxide in viral pneumonia due to COVID-19: a randomised clinical study.

High-dose inhaled Nitric Oxide (iNO) has been shown to have anti-inflammatory, vasodilator, and antimicrobial properties, resulting in improved arterial oxygenation as well as a beneficial therapeutic effect on lower respiratory tract infections. This study evaluated the safety and efficacy of 150-ppm intermittent iNO administered with a novel iNO-generator, for treating adults hospitalised for viral pneumonia. In this prospective, open-label, multicenter study, subjects aged 18-80, diagnosed with viral pneumonia received either standard supportive treatment alone (Control-Group) or combined with iNO for 40 min, 4 times per day up to 7 days (Treatment-Group).

The SIRT7-nucleolus connection in cancer: ARF enters the fray.

The nucleolar enzyme sirtuin 7 (SIRT7) promotes cancer progression in certain malignancies, likely in part by controlling ribosome biosynthesis. Recently, we discovered that SIRT7 destabilizes the cyclin dependent kinase inhibitor 2A (CDKN2A, known as ARF) within the nucleolus, aiding cancer progression. We propose that targeting nucleolar SIRT7 offers promise for new anti-cancer therapies.

Phenotypical characteristics of nontuberculous mycobacterial infection in patients with bronchiectasis.

Background: The global mortality and morbidity rates of bronchiectasis patients due to nontuberculous mycobacteria (NTM) pulmonary infection are on a concerning upward trend. The aims of this study to identify the phenotype of NTM-positive individuals with bronchiectasis.

Methods: A retrospective single-center observational study was conducted in adult patients with bronchiectasis who underwent bronchoscopy in 2007-2020.

[Harmful health effects of flavors in e-cigarettes].

Background: Almost all e-cigarettes contain flavorings that make the product more attractive. In the evaluation of e-cigarettes on health, flavors have so far played a subordinate role.

Method: Selective literature search in PubMed, supplemented by legal regulations on the use of flavors in e-cigarettes.

Effect of Supplemental Oxygen on Physiological Responses to Exercise in Fibrotic Interstitial Lung Disease.

Purpose: We studied the effect of O 2 supplementation on physiological response to exercise in patients with moderate to severe interstitial lung disease (ILD).

Methods: Thirteen patients (age 66 ± 10 yr, 7 males) with ILD (total lung capacity, 71% ± 22% predicted; carbon monoxide diffusion capacity, 44% ± 16% predicted) and 13 healthy individuals (age 50 ± 17 yr, 7 males) were tested. ILD patients performed symptom-limited cardiopulmonary exercise tests and constant work rate (WR) tests at 80% of the WR at the gas exchange threshold.