dEREGulated pathways: Unraveling the role of epiregulin in skin, kidney and lung fibrosis.

The epidermal growth factor receptor (EGFR) signaling pathway is an evolutionary conserved mechanism to control cell behavior during tissue development and homeostasis. Deregulation of this pathway has been associated with abnormal cell behavior, including hyperproliferation, senescence, and an inflammatory cell phenotype, thereby contributing to pathologies across a variety of organs, including kidney, skin, and lung. To date, there are seven distinct EGFR ligands described.

Targeting pleuro-alveolar junctions reverses lung fibrosis in mice.

Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium.

High-Affinity Lectin Ligands Enable the Detection of Pathogenic Biofilms: Implications for Diagnostics and Therapy.

is a critical priority pathogen and causes life-threatening acute and biofilm-associated chronic infections. The choice of suitable treatment for complicated infections requires lengthy culturing for species identification from swabs or an invasive biopsy. To date, no fast, pathogen-specific diagnostic tools for infections are available.

An overview of climate changes and its effects on health - from mechanisms to One Health.

Human activities, primarily the burning of fossil fuels, widespread deforestation, soil erosion or machine-intensive farming methods, manufacturing, food processing, mining, and construction iron, cement, steel, and chemicals industry, have been the main drivers of the observed increase in Earth's average surface temperature and climate change. Rising global temperatures, extreme weather events, ecosystems disruption, agricultural impacts, water scarcity, problems in access to good quality water, food and housing, and profound environmental disruptions such as biodiversity loss and extreme pollution are expected to steeply increase the prevalence and severity of acute and chronic diseases. Its long-term effects cannot be adequately predicted or mitigated without a comprehensive understanding of the adaptive ecosystems.

Impact of absolute values and changes in meteorological and air quality conditions on community-acquired pneumonia in Germany.

Community-acquired pneumonia (CAP) is a major global health concern as it is a leading cause of morbidity, mortality and economic burden to the health care systems. In Germany, more than 15,000 people die every year from CAP. Climate change is altering weather patterns, and it may influence the probability and severity of CAP.

Prognostic value of metabolic tumor volume on [F]FDG PET/CT in addition to the TNM classification system of locally advanced non-small cell lung cancer.

Purpose: Staging of non-small cell lung cancer (NSCLC) is commonly based on [F]FDG PET/CT, in particular to exclude distant metastases and guide local therapy approaches like resection and radiotherapy. Although it is hoped that PET/CT will increase the value of primary staging compared to conventional imaging, it is generally limited to the characterization of TNM. The first aim of this study was to evaluate the PET parameter metabolic tumor volume (MTV) above liver background uptake as a prognostic marker in lung cancer.

Assessing the comparative effects of interventions in COPD: a tutorial on network meta-analysis for clinicians.

To optimize patient outcomes, healthcare decisions should be based on the most up-to-date high-quality evidence. Randomized controlled trials (RCTs) are vital for demonstrating the efficacy of interventions; however, information on how an intervention compares to already available treatments and/or fits into treatment algorithms is sometimes limited. Although different therapeutic classes are available for the treatment of chronic obstructive pulmonary disease (COPD), assessing the relative efficacy of these treatments is challenging.

Post-coronavirus disease 2019-associated symptoms among children and adolescents in the SARS-CoV-2 Omicron era.

Purpose: Lack of a control group(s) and selection bias were the main criticisms of previous studies investigating the prevalence of post-coronavirus disease 2019 (COVID-19) syndrome (PCS). There are insufficient data regarding paediatric PCS, particularly in the SARS-CoV-2 Omicron era. As such, our study investigated PCS-associated symptoms in a representative control-matched cohort.

The epithelial era of asthma research: knowledge gaps and future direction for patient care.

The Epithelial Science Expert Group convened on 18-19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated.

GOLD COPD Exacerbation History Categories and Disease Outcomes.

Importance: Previous exacerbations of chronic obstructive pulmonary disease (ECOPD) are associated with future events. For more than a decade, patients at high risk have been defined as individuals with a history of 2 or more moderate ECOPD, 1 or more severe ECOPD, or both within 12 months, and treatments have been allocated accordingly, but these cutoffs lack validation.

Objectives: To validate ECOPD history categories by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and explore alternative cutoffs to estimate moderate and severe ECOPD and all-cause mortality in COPD.

Early career member highlights from the 22nd ERS Lung Science Conference: development of chronic lung diseases - from life-spanning mechanisms to preventive therapy.

https://bit.ly/4cbMjpS.

Clinical Implementation of a High-Throughput Automated Comprehensive Genomic Profiling Test: TruSight Oncology 500 HT.

The adoption of comprehensive genomic profiling in oncology has rapidly increased the demand for standardized tumor sample processing in diagnostic laboratories. Automation of DNA and RNA library preparation workflows offers the possibility to scale-up and standardize sample processing. We report on the clinical implementation of the automated TruSight Oncology 500 High-Throughput library preparation workflow from formalin-fixed, paraffin-embedded tumor samples using the Biomek i7 hybrid Workstation.

Considerations for building and using integrated single-cell atlases.

The rapid adoption of single-cell technologies has created an opportunity to build single-cell 'atlases' integrating diverse datasets across many laboratories. Such atlases can serve as a reference for analyzing and interpreting current and future data. However, it has become apparent that atlasing approaches differ, and the impact of these differences are often unclear.

Riociguat in pulmonary arterial hypertension: Application of the 4-strata COMPERA 2.0 risk assessment tool in the PATENT studies.

Background: Risk stratification is an essential part of evaluating disease severity in patients with pulmonary arterial hypertension (PAH). This study applied the 4-strata COMPERA 2.0 risk model to the Phase 3 PATENT-1/2 studies of riociguat.

ATP citrate lyase drives vascular remodeling in systemic and pulmonary vascular diseases through metabolic and epigenetic changes.

ATP citrate lyase (ACLY), a crucial enzyme in de novo lipid synthesis and histone acetylation, plays a key role in regulating vascular smooth muscle cell (VSMC) proliferation and survival. We found that human coronary and pulmonary artery tissues had up-regulated ACLY expression during vascular remodeling in coronary artery disease and pulmonary arterial hypertension. Pharmacological and genetic inhibition of ACLY in human primary cultured VSMCs isolated from the coronary arteries of patients with coronary artery diseases and from the distal pulmonary arteries of patients with pulmonary arterial hypertension resulted in reduced cellular proliferation and migration and increased susceptibility to apoptosis.

Nasal secretions trace epithelial type 2 response to allergen-specific immunotherapy.

Background: Allergen-specific immunotherapy (AIT) is a disease-modifying therapy and is effective to reduce the symptoms of grass pollen-allergy. The airway epithelium of these patients releases inflammatory mediators including type-2 cytokines, which are associated with cellular processes involved in the symptomatic response of the affected tissue. Aim of the study was to identify epithelial biomarkers indicating AIT progress.

Occupational anaphylaxis: A Position Paper of the German Society of Allergology and Clinical Immunology (DGAKI).

Background: Anaphylaxis is a systemic allergic reaction that is potentially life-threatening. Occupational anaphylaxis is an anaphylaxis that occurs in an occupational context. In this position paper, we propose diagnostic criteria for occupational anaphylaxis and provide an overview of the current state of knowledge in terms of prevalence, triggers, prevention, and management.

Revival of recombinant IL-2 therapy - approaches from the past until today.

Interleukin-2 (IL-2) was one of the first cytokines discovered and its central role in T cell function soon led to the notion that the cytokine could specifically activate immune cells to combat cancer cells. Recombinant human IL-2 (recIL-2) belonged to the first anti-cancer immunotherapeutics that received marketing authorization and while it mediated anti-tumor effects in some cancer entities, treatment was associated with severe and systemic side effects. RecIL-2 holds an exceptional therapeutic potential, which can either lead to stimulation of the immune system - favorable during cancer treatment - or immunosuppression - used for treatment of inflammatory diseases such as autoimmunity.

Type 2 responses determine skin rash during recombinant interleukin-2 therapy.

The skin is the organ most often affected by adverse drug reactions. Although these cutaneous adverse drug reactions (CADRs) often are mild, they represent a major burden for patients. One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy.

Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways.

This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case.

SPARCL1 and NT-proBNP as biomarkers of right ventricular-to-pulmonary artery uncoupling in pulmonary hypertension.

Aims: SPARCL1 was recently identified as a biomarker of right ventricular (RV) maladaptation in patients with pulmonary hypertension (PH), and N-terminal pro-brain natriuretic protein (NT-proBNP) is an established biomarker of RV failure in PH. The present study investigated whether NT-proBNP and SPARCL1 concentrations are associated with load-independent parameters of RV function and RV-to-pulmonary artery (RV-PA) coupling as measured using invasive pressure-volume (PV) loops in the RV.

Methods: SPARCL1 and NT-proBNP were measured in the plasma of patients with idiopathic pulmonary artery hypertension (IPAH, n = 73).

Fractionated stereotactic radiotherapy of brainstem metastases - Clinical outcome and prognostic factors.

Introduction: Brain metastases (BM) are the most common malignancy in the central nervous system (CNS) and observed in approximately 30% of cancer patients. Brainstem metastases (BSM) are challenging because of their location and the associated neurological risks. There are still no general therapeutic recommendations in this setting.

Association of Patients' Knowledge on the Disease and Its Management with Indicators of Disease Severity and Individual Characteristics in Patients with Chronic Obstructive Pulmonary Disease (COPD): Results from COSYCONET 2.

Background: In patients with chronic diseases, including those with chronic obstructive pulmonary disease (COPD), knowledge on the disease and its self-management is considered as relevant for improving disease control and long-term outcome. We studied to which extent components of knowledge depended on potential predictors, such as participation in educational programs and disease severity. For example, the perception of exacerbations or GOLD grade might modulate the content and reliability of COPD understanding.