Publications by authors named "Witzenrath M"

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.

View Article and Find Full Text PDF

Background: Existing risk evaluation tools underperform in predicting intensive care unit (ICU) admission for patients with the 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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF
Article Synopsis
  • This study focuses on the role of Thyroid Transcription Factor-1 (TTF-1) in lung adenocarcinoma (LUAD) brain metastases, specifically its predictive value and relationship with patient outcomes.
  • Researchers analyzed data from 245 patients who had brain metastases, looking at factors like tumor volume and survival rates based on TTF-1 expression status.
  • Results indicate that TTF-1 negative patients had larger tumors, higher proliferation rates, and worse survival outcomes, suggesting that TTF-1 negativity signifies a more aggressive form of the disease, warranting further study on its underlying mechanisms.
View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF
Article Synopsis
  • Hypernatremia is a common and serious condition in ICU patients, linked to higher mortality and longer stays, prompting this study to compare sodium chloride 0.9% and glucose 5% solutions as intravenous drug diluents.
  • The study analyzed 265 adult COVID-19 patients, observing sodium levels and severe hypernatremia over the first 8 days after ICU admission, finding that glucose 5% led to lower sodium levels and reduced occurrences of severe hypernatremia.
  • The results suggest that switching to glucose 5% as the standard diluent can help prevent hypernatremia in ICU patients, indicating a potentially simple change in treatment protocols.
View Article and Find Full Text PDF

Background: Patients with post-COVID-19 condition frequently suffer from chronic dyspnoea. The causes and mechanism for dyspnoea in these patients without evidence of structural lung disease are unclear.

Methods: Patients treated for COVID-19 at Charité University Hospital in Berlin received pulmonary function testing including respiratory muscle strength tests and completed health-related quality-of-life questionnaires during follow-up.

View Article and Find Full Text PDF
Article Synopsis
  • Endoscopic lung volume reduction (ELVR) with endobronchial valves (EBV) is a treatment for severe COPD patients suffering from emphysema and hyperinflation, but it may lead to complications like infections.
  • A study of ten COPD patients who had EBV removed revealed the presence of bacterial infections and biofilms on the valves, which could contribute to worsening symptoms and increased exacerbations.
  • The findings highlight the need for further research to understand the role of these infections and develop treatments to prevent them in patients undergoing ELVR.
View Article and Find Full Text PDF

Background: Translating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses.

Methods: Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution.

View Article and Find Full Text PDF

In the early phase of the COVID-19 pandemic, many local collections of clinical data on patients infected with SARS-CoV-2 were initiated in Germany. As part of the National Pandemic Cohort Network (NAPKON) of the University Medicine Network, the "Integration Core" was established to design the legal, technical and organisational requirements for the integration of inventory data into ongoing prospective data collections and to test the feasibility of the newly developed solutions using use cases (UCs). Detailed study documents of the data collections were obtained.

View Article and Find Full Text PDF

Background: Health-related quality of life (HRQL) has become an important outcome parameter in cardiology. The MOS 36-ltem Short-Form Health Survey (SF-36) and the PROMIS-29 are two widely used generic measures providing composite HRQL scores. The domains of the SF-36, a well-established instrument utilized for several decades, can be aggregated to physical (PCS) and mental (MCS) component summary scores.

View Article and Find Full Text PDF

The pulmonary epithelial glycocalyx is rich in glycosaminoglycans such as hyaluronan and heparan sulfate. Despite their presence, the importance of these glycosaminoglycans in bacterial lung infections remains elusive. To address this, we intranasally inoculated mice with in the presence or absence of enzymes targeting pulmonary hyaluronan and heparan sulfate, followed by characterization of subsequent disease pathology, pulmonary inflammation, and lung barrier dysfunction.

View Article and Find Full Text PDF
Article Synopsis
  • The study examined how often and significantly Herpes simplex virus (HSV) reactivates in patients with community-acquired pneumonia (CAP) and identified potential risk factors.
  • It analyzed data from adult CAP patients in the CAPNETZ study (2007-2017), where both sputum and blood samples were tested for HSV, focusing on demographics and clinical outcomes.
  • Results showed that HSV-1 was present in 12.2% of patients, but its presence didn’t correlate with worse outcomes, suggesting that while HSV reactivation is common, it may not complicate the disease significantly.
View Article and Find Full Text PDF

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes.

View Article and Find Full Text PDF

A key issue for research on COVID-19 pathogenesis is the lack of biopsies from patients and of samples at the onset of infection. To overcome these hurdles, hamsters were shown to be useful models for studying this disease. Here, we further leverage the model to molecularly survey the disease progression from time-resolved single-cell RNA sequencing data collected from healthy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected Syrian and Roborovski hamster lungs.

View Article and Find Full Text PDF

Background: Community-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated restrictions effectively reduced the circulation of CARVs.

View Article and Find Full Text PDF

IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to lung infection than wild-type animals and that single-nucleotide polymorphisms in and were associated with pneumococcal pneumonia in humans. The effect of IL-33 on infection was mediated by negative regulation of IL-22 production in innate lymphoid cells (ILCs) but independent of ILC2s as well as IL-4 and IL-13 signaling.

View Article and Find Full Text PDF

Purpose: Coronavirus disease 2019 (COVID-19) and non-COVID-19 community-acquired pneumonia (NC-CAP) often result in hospitalization with considerable risks of mortality, ICU treatment, and long-term morbidity. A comparative analysis of clinical outcomes in COVID-19 CAP (C-CAP) and NC-CAP may improve clinical management.

Methods: Using prospectively collected CAPNETZ study data (January 2017 to June 2021, 35 study centers), we conducted a comprehensive analysis of clinical outcomes including in-hospital death, ICU treatment, length of hospital stay (LOHS), 180-day survival, and post-discharge re-hospitalization rate.

View Article and Find Full Text PDF

Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers.

View Article and Find Full Text PDF