Subdomains of Post-COVID Syndrome (PCS) - a population-based study.

Purpose: 'Post-COVID Syndrome' (PCS), which encompasses the multifaceted sequelae of COVID-19, can be severity-graded by a previously defined score encompassing 12 different long-term symptom complexes. The PCS score was shown to have two main predictors, namely acute COVID-19 severity and individual resilience. The purpose of the present study was to verify these predictors and to assess their detailed relationship to the symptom complexes constituting the PCS score.

Endothelin-1 in combination with CRB-65 enhance risk stratification in COVID-19 patients.

Background: COVID-19 continuously causes severe disease conditions and significant mortality. We evaluate whether easily accessible biomarkers can improve risk prediction of severe disease outcomes.

Methods: Our study analysed 426 COVID-19 patients collected by German CAPNETZ and PROGRESS study groups between 2020 and 2021.

Best Practices in the Development and Use of Experimental Models of Bacterial Pneumonia: An Official American Thoracic Society Workshop Report.

The global incidence of respiratory infectious diseases caused by bacteria continues to increase, with acute lower respiratory tract infections contributing to significant morbidity and mortality. Preclinical models designed to investigate such respiratory bacterial diseases are of utmost importance to decipher their pathogenesis and develop novel targets for intervention and treatment. Animal models offer the powerful ability to investigate different pneumonia types at varying stages of infection and disease.

Multicentre pragmatic embedded stepped wedge cluster randomised trial comparing glucose 5% with sodium chloride 0.9% as the default drug diluent in the ICU: the sweet-water trial protocol.

Introduction: Hypernatraemia, defined as a plasma sodium concentration >145 mmol/L, is a frequent complication in critically ill patients treated in the intensive care unit (ICU) (= ICU-acquired hypernatraemia), with reported prevalence ranging from 4% to 26%. Hypernatraemia adversely affects various physiological functions and is associated with delirium, prolonged length of stay and increased ICU and post-discharge mortality. The sodium load from intravenous drug diluents significantly contributes to ICU-acquired hypernatraemia, with drug infusions comprising about 30% of the daily fluid volume of an average ICU patient.

Managing withdrawals and exclusions of study participants in COVID-19-research by NUKLEUS.

Background: This article describes how withdrawals and exclusions of study participants can be managed in COVID-19-cohort studies by NUKLEUS (German: NUM Klinische Epidemiologie- und Studienplattform), using NAPKON (German: Nationales Pandemie Kohorten Netz). The aim of this manuscript was to describe, how partial withdrawals can be performed so that most of the data and bio-samples can be kept for research purposes.

Methods: The study has taken all signed informed consents (ICs) of study participants into account in order to develop a method how partial withdrawals can be developed and installed.

Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa.

Bacterial multidrug resistance poses an urgent challenge for the treatment of critically ill patients developing ventilator-associated pneumonia (VAP). Phage therapy, a potential alternative when conventional antibiotics fail, has been unsuccessful in first clinical trials when used alone. Whether combining antibiotics with phages may enhance effectiveness remains to be tested in experimental models.

Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany.

If health impairments due to coronavirus disease 2019 (COVID-19) persist for 12 weeks or longer, patients are diagnosed with Post-COVID Syndrome (PCS), or Long-COVID. Although the COVID-19 pandemic has largely subsided in 2024, PCS is still a major health burden worldwide, and identifying potential genetic modifiers of PCS remains of great clinical and scientific interest. We therefore performed a case-control type genome-wide association study (GWAS) of three recently developed PCS (severity) scores in 2,247 participants of COVIDOM, a prospective, multi-centre, population-based cohort study of SARS-CoV-2-infected individuals in Germany.

Phage-phage competition and biofilms affect interactions between two virulent bacteriophages and Pseudomonas aeruginosa.

Virulent bacteriophages (or phages) are viruses that specifically infect and lyse a bacterial host. When multiple phages co-infect a bacterial host, the extent of lysis and dynamics of bacteria-phage and phage-phage interactions are expected to vary. The objective of this study is to identify the factors influencing the interaction of two virulent phages with different Pseudomonas aeruginosa growth states (planktonic, an infected epithelial cell line, and biofilm) by measuring the bacterial time-kill and individual phage replication kinetics.

DNA methylation changes during acute COVID-19 are associated with long-term transcriptional dysregulation in patients' airway epithelial cells.

Molecular changes underlying the persistent health effects after SARS-CoV-2 infection remain poorly understood. To discern the gene regulatory landscape in the upper respiratory tract of COVID-19 patients, we performed enzymatic DNA methylome and single-cell RNA sequencing in nasal cells of COVID-19 patients (n = 19, scRNA-seq n = 14) and controls (n = 14, scRNA-seq n = 10). In addition, we resampled a subset of these patients for transcriptome analyses at 3 (n = 7) and 12 months (n = 5) post infection and followed the expression of differentially regulated genes over time.

[Focus: artificial intelligence in medicine-Legal aspects of using large language models in clinical practice].

Background: The use of artificial intelligence (AI) and natural language processing (NLP) methods in medicine, particularly large language models (LLMs), offers opportunities to advance the healthcare system and patient care in Germany. LLMs have recently gained importance, but their practical application in hospitals and practices has so far been limited. Research and implementation are hampered by a complex legal situation.

Cell Surface RNA Expression Modulates Alveolar Epithelial Function.

Glycosylated RNA (glycoRNA) has recently emerged as a novel constituent of the glycocalyx on cell surfaces, yet its biological functions remain largely unexplored. In this report, we present the first analysis of glycoRNA expression and functionality in alveolar epithelial cells. To this end, we optimized new techniques for the detection of glycoRNA on living cell surfaces and in cell membrane-associated RNA samples through in-gel imaging after labeling with fluorescent dye conjugates.

Clinical safety and pharmacokinetics of a novel oral niclosamide formulation compared with marketed niclosamide chewing tablets in healthy volunteers: A three-part randomized, double-blind, placebo-controlled trial.

Aim: Niclosamide is an established anthelmintic substance and a promising candidate for treating cancer, viral infections, and other diseases. However, its solubility in aqueous media is low, and the systemic bioavailability of the commercially available chewing tablet is poor, limiting the use of niclosamide for systemic treatment. A liquid oral formulation using polyethylene glycol 400 was developed and investigated in healthy volunteers to assess safety, tolerability, and pharmacokinetics in comparison to the marketed tablet.

Comparing viral, bacterial, and coinfections in community-acquired pneumonia, a retrospective cohort study.

Objectives: Despite the substantial rates of viral etiology in community-acquired pneumonia (CAP), empirical antibiotic therapy is regularly administered. This study compared the clinical presentation, antibiotic use, and outcomes of patients based on the identified causative pathogens.

Methods: Patients that were immunocompetent and had CAP from the international, multicenter prospective cohort study on CAP (CAPNETZ) from 2007 to 2017 with available multiplex polymerase chain reaction testing for bacterial and viral pathogens from sputum were included.

Pulmonary vascular remodeling in Fra-2 transgenic mice is driven by type 2 inflammation and accompanied by pulmonary vascular hyperresponsiveness.

Lung vessel remodeling leads to increased pulmonary vascular resistance, causing pulmonary arterial hypertension (PAH), and consequently right ventricular hypertrophy and failure. In patients suffering from systemic sclerosis (SSc), PAH can occur and is a life-threatening complication. Dysregulation of immune processes plays a crucial role in pulmonary vascular remodeling, as has previously been shown in Fos-related antigen-2 (Fra-2) transgenic (TG) mice, a model of SSc-PAH.

Clinical improvements after endoscopic lung volume reduction with valves in patients with advanced emphysema and a 6-min walk test ≤140 m at baseline.

Background: Data regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with a very low 6-min walk test (6MWT) are limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutic benefits and increased complication risk.

Study Designs And Methods: This study utilised data from the Lungenemphysemregister e.

Predicting the Risk of Intensive Care Unit Admission in Patients With COVID-19 Presenting in the Emergency Room: Development and Evaluation of the Confusion, Respiratory Rate, Oxygen Saturation With or Without Concurrent Supplemental Oxygen, and Oxygen Supplementation Score.

Background: Existing risk evaluation tools underperform in predicting intensive care unit (ICU) admission for patients with coronavirus disease 2019 (COVID-19). This study aimed to develop and evaluate an accurate and calculator-free clinical tool for predicting ICU admission at emergency room (ER) presentation.

Methods: Data from patients with COVID-19 in a nationwide German cohort (March 2020-January 2023) were analyzed.

Diabetes impairs IFNγ-dependent antibacterial defense in the lungs.

Diabetes mellitus is associated with an increased risk of pneumonia, often caused by so-called typical and atypical pathogens including Streptoccocus pneumoniae and Legionella pneumophila, respectively. Here, we employed a variety of mouse models to investigate how diabetes influences pulmonary antibacterial immunity. Following intranasal infection with S.

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.

A biomathematical model of SARS-CoV-2 in Syrian hamsters.

When infected with SARS-CoV-2, Syrian hamsters (Mesocricetus auratus) develop moderate disease severity presenting key features of human COVID-19. We here develop a biomathematical model of the disease course by translating known biological mechanisms of virus-host interactions and immune responses into ordinary differential equations. We explicitly describe the dynamics of virus population, affected alveolar epithelial cells, and involved relevant immune cells comprising for example CD4+ T cells, CD8+ T cells, macrophages, natural killer cells and B cells.

Semisynthetic Glycoconjugate Vaccine Lead against Serotype O2afg Induces Functional Antibodies and Reduces the Burden of Acute Pneumonia.

Carbapenem-resistant (CR-) bacteria are a serious global health concern due to their drug-resistance to nearly all available antibiotics, fast spread, and high mortality rate. O2afg is a major CR- serotype in the sequence type 258 group (KPST258) that is weakly immunogenic in humans. Here, we describe the creation and evaluation of semisynthetic O2afg glycoconjugate vaccine leads containing one and two repeating units of the polysaccharide epitope that covers the surface of the bacteria conjugated to the carrier protein CRM.

Biomarkers troponin and procalcitonin in addition to CRB-65 enhance risk stratification in patients with community-acquired pneumonia.

Background: Community-acquired pneumonia (CAP) remains a leading cause of infectious disease mortality globally, necessitating intensive care unit (ICU) admission for ∼10% of hospitalised patients. Accurate prediction of disease severity facilitates timely therapeutic interventions.

Methods: Our study aimed to enhance the predictive capacity of the clinical CRB-65 score by evaluating eight candidate biomarkers: troponin T high-sensitive (TnT-hs), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide, angiopoietin-2, copeptin, endothelin-1, lipocalin-2 and mid-regional pro-adrenomedullin.

Comparison of Efficacy and Safety of Different Types of One-Way Valves in Endoscopic Lung Volume Reduction in Patients with Severe Lung Emphysema.

Introduction: Endoscopic lung volume reduction (ELVR) with valves is an effective intervention in patients with severe lung emphysema. Two types of valves are established in clinical practice: Zephyr endobronchial valves (EBVs) and Spiration Valve System (SVS). We aimed to compare outcomes and the safety associated with these two types of one-way valves.