University Hospital Bonn

Worldwide, billions of day-old male chicks are culled each year in the egg industry due to the low market value of layer-type males. As a result of public pressure on this ethical issue, some countries banned the practice, leading to changes in animal welfare legislation. In addition to the use of dual-purpose chicken for egg and meat production, technologies for in-ovo sex determination, aiming to cull male embryos during early development and prior to the onset of pain perception, are feasible alternatives. However, the temporal onset of pain perception in chick embryos is still unknown, and its determination is challenging. Here we embed a review of the existing literature of in-ovo pain research under the country-specific umbrella of societal discussions and culling alternatives. Recently, a study on nociception measured first signs of responses by the embryo at day 13 of incubation. Still, neither the depiction of nociceptive pathways nor an EEG, which includes signals of general muscle contraction, provide definitive proof of the perception of pain. We urge that more knowledge about the development of pain perception in chick embryos is key to the ethical framework that should underpin policy decisions.

Social media have proliferated globally, with an estimated 5.1-5.5billion active users and are gaining increasing relevance in anesthesiology. Social media are now firmly established as amedium for knowledge acquisition and information retrieval. In this context, "medfluencers" (individuals and institutions) play agrowing role in disseminating health-related and discipline-specific information. The aim of this article is firstly, to develop aclearer understanding of "medfluencers" in anesthesiology and secondly, to synthesize the opportunities and risks of social media for anesthesiology through astructured literature analysis. Following specification of the two core research questions, asystematic literature search was conducted using predefined search strings in PubMed. Relevant contents from identified publications were synthesized into atypology of "medfluencers" and/or opportunities and risks of social media in anesthesiology. The literature search was performed in asystematic PRISMA-oriented manner and due to the heterogeneity of study designs and outcomes a narrative synthesis of the evidence was carried out. Atotal of 1727 possible publications were identified and after the screening process 49 articles (original studies and reviews) were included. From the results five types of "medfluencers" in anesthesiology with distinct competencies, resources and aims were delineated. Social media activities in anesthesiology were synthesized into six opportunities and six risks for the respective "medfluencer" groups. Virality is not aproxy for quality. Simultaneously, social media create a broad coverage and therefore entail content, ethical and legal responsibility. The use of social media offers novel possibilities for anesthesiology but requires acritical, evidence-based and legally compliant utilization. Concrete mitigation strategies to minimize risks are discussed, from which practical dos and don'ts for "medfluencers" are derived. Further studies are needed to be able to assess the effects on specific anesthesiological practices and the impacts on patient outcomes.

Liver cirrhosis profoundly alters pharmacokinetics and is frequently associated with medication-related problems. Stage-specific dosing guidance remains inconsistent, and prescribing information often lacks clarity. As a result, treatment decisions rely on individual clinical judgement and may differ between professional groups. This study assessed drug-selection and dose-adjustment practices among hepatologists, clinical pharmacologists, and clinical pharmacists, quantified consensus across Child-Pugh stages, and evaluated alignment with prescribing information as a basis for harmonised dosing guidance. Twelve experts from hepatology, clinical pharmacology, and clinical pharmacy evaluated prioritised drugs for patients with liver cirrhosis across Child-Pugh stages A-C in a structured survey. For each drug, experts indicated whether they would apply no dose adjustment, modify the dose, or avoid administration. Consensus was defined as at least 75% agreement, and interrater agreement was assessed by pairwise percentage agreement. Consensus recommendations were compared with the dosing information provided in each drug's Summary of Product Characteristics. Consensus or strong consensus was achieved for only 20% of 177 recommendations, mainly for no dose adjustment or avoidance. Agreement decreased with disease severity (Child-Pugh A 83%; B 47%; C 41%). Of 36 consensus recommendations, 18 matched the summary of product characteristics, while six diverged from it. Pharmacists and clinical pharmacologists more often recommended dose adjustments, especially in Child-Pugh B and C, whereas hepatologists preferred standard dosing or avoidance. Expert recommendations for dosing in cirrhosis showed marked variability and limited concordance with prescribing information, underscoring the need for harmonised interdisciplinary guidance integrating pharmacokinetic evidence and clinical feasibility.

Zusammenfassung Hintergrund Die neonatale Enzephalopathie (NE) nach perinataler Asphyxie ist eine der Hauptursachen für Neugeborenensterblichkeit und für neurologische Langzeitschäden. Die therapeutische Hypothermie (TH) stellt die einzige etablierte Therapie für Neugeborene mit moderater bis schwerer NE dar. Trotz dieser Therapie besteht ein hohes Risiko für bleibende neurologische Beeinträchtigungen. Frühzeitige Aussagen über das Langzeit-Outcome sind hilfreich, um therapeutische Entscheidungen zu treffen, frühzeitig neuroprotektive und -rehabilitative Maßnahmen einzuleiten und die betroffene Familie zu beraten. Ziel In diesem Übersichtsartikel möchten wir einen Überblick über mögliche Prognoseparameter des Langzeit-Outcome asphyktischer Neugeborener nach TH geben. Methoden Wir bewerten mögliche Prognoseparameter systematisch, um abschließend eine klinisch anwendbare Vorgehensweise zu entwickeln und das Langzeit-Outcome nach TH möglichst zuverlässig einschätzen zu können. Ergebnisse Zuverlässige Prognoseparameter nach TH sind eine ausbleibende Normalisierung des (a) EEG nach 48 h, ein dauerhaftes Ausbleiben eines Schlaf-Wach-Rhythmus im (a) EEG, das Vorliegen eines Status epilepticus im (a) EEG sowie spezifische Auffälligkeiten in bildgebenden Untersuchungen (Schädelsonographie und MRT). Standardisierte klinisch-neurologische Untersuchungen besitzen insbesondere für das motorische Outcome eine hohe Aussagekraft. Parameter der ersten Lebensstunden wie 1‑min-, 5‑min- und 10-min-Apgar-Index, pH-Wert und Sarnat‑/Thompson-Score erlauben keine Aussage über das Langzeit-Outcome, helfen aber jene Neugeborenen zu identifizieren, die mittels TH behandelt werden sollten. Diskussion Die Langzeitprognose nach TH sollte in der Zusammenschau verschiedener klinischer und apparativer Untersuchungen erfolgen.

Inflammation is a key driver of hematopoietic dysfunction in myeloid malignancies, but its role in the context of hypomethylating therapy remains incompletely understood. Although 5-Azacytidine is used posttransplant in high-risk myelodysplastic syndrome (MDS), only 50% of patients show a clinical response. We provide evidence that inherent inflammatory properties of healthy donor CD34+ stem cells exist that are likely to contribute to the "response" seen in MDS patients. These are linked to epigenetic priming of the myeloid niche, resulting in an S100A8/A9-driven inflammatory program that promotes functionality of immature NK cells. Using in vitro differentiation systems, multi-omic profiling, and an S100A9-/- mouse model, we find that 5-AzaC modulates inflammatory transcriptional programs through epigenetic rewiring of upstream regulatory elements. Loss of S100A9 disrupts myeloid differentiation, impairs NK cell maturation, and alters key developmental regulators including CEBPB, JUN, and NFIL3. In vivo, 5-AzaC restores these defects and primes NK cells in a time- and context-dependent manner. Re-analysis of the published Australian MDS/CMML cohort shows that "responders" display increased S100A8/A9 expression together with enhanced IFN-gamma, IL6-JAK-STAT3, and TNF signaling. These findings suggest that inflammatory myeloid programs may serve as predictive biomarkers and therapeutic targets to enhance NK cell-mediated graft-versus-leukemia activity posttransplant.

Avelumab, pembrolizumab, and enfortumab vedotin (EV) demonstrated efficacy in mUC following platinum-based chemotherapy. However, real-world data in patients with urothelial carcinoma with squamous differentiation (UCSD) are limited. The aim of this study is to assess the real-world clinical outcomes of avelumab, pembrolizumab, or EV in mUCSD patients. The ARON-2EV study is a retrospective, international, multicenter analysis in patients with mUC treated with avelumab, pembrolizumab, or EV across 79 centers in 21 countries. Patients were divided into three cohorts: 1 (avelumab), 2 (pembrolizumab), and 3 (EV). Primary endpoints were overall survival (OS) and time on treatment (ToT). Secondary objectives included evaluating clinical factors associated with outcomes and exploring the impact of UCSD histology on response to therapy. Statistical methods included Kaplan-Meier estimates, log-rank tests, Fisher's exact and chi-square tests, and Pearson's correlation coefficients. A total of 1918 patients, 1696 with advanced pure UC (pUC) and 222 with mUCSD (36 in cohort 1, 111 in cohort 2, and 75 in cohort 3), were included. Median OS was shorter in patients with UCSD compared to patients with pUC histology in the three cohorts (1: 13.0 vs 26.8months, HR 2.66,p = 0.003; 2: 10.2 vs 18.5months, HR 1.52,p = 0.008; and 3: 7.6 vs 13.1months, HR 1.68,p = 0.011). Median ToT was shorter in patients with UCSD compared to patients with pUC histology in cohort 1 (3.5 vs 5.6months, HR 1.57,p = 0.044) and 3 (7.6 vs 13.6months, HR 1.83,p = 0.005) but not in cohort 2 (3.7 vs 4.7months, HR 1.19,p = 0.177). Response to therapy was negatively correlated with UCSD histology in cohorts 2 (correlation coefficient 0.094,p = 0.008) and 3 (correlation coefficient 0.107,p = 0.021), while response to avelumab was not correlated with UCSD (correlation coefficient 0.072,p = 0.263). UCSD is a histology with a poor prognosis and response to treatments compared to pUC. Treatments activity and effectiveness in divergent differentiations should be addressed in dedicated prospective studies. NCT05290038.

The S2K guideline, organized by the German Respiratory Society, is aimed at physicians in Germany, Switzerland, and Austria who perform outpatient or inpatient diagnostic flexible bronchoscopy in adult patients. Its goal is to standardize the procedure, minimize complications, and improve diagnostic safety. The guideline specifically addresses specialists in pulmonology, thoracic surgery, and hospital hygiene, as well as nursing and technical staff. It provides evidence- and consensus-based recommendations on indications, preparation, execution, hygiene measures, and aftercare. Additionally, it serves as an information resource for physicians from other specialties, payers, professional societies, and can support quality management. It applies to medical care in Germany, Austria, and Switzerland and incorporates the latest scientific findings up to the date of publication.

To evaluate the association of hyperreflective foci contiguous with the retinal pigment epithelium (rpeHRF) with visual function impairment in aged normals, early age-related macular degeneration (eAMD), and intermediate AMD (iAMD). Prospective cohort study. Participants of the MACUSTAR study. MACUSTAR participants underwent color fundus photography, optical coherence tomography (OCT) imaging, best corrected visual acuity (BCVA), low-luminance VA (LLVA), rod-mediated dark adaptation (RMDA) at 12°, contrast sensitivity (CS), mesopic (mesPSD), and scotopic pointwise sensitivity deviation (scPSD) testing. rpeHRF presence and count were determined using custom FiJi software. Group comparisons and associations with visual function were analyzed using analysis of variance, linear regression, and Spearman correlation. Presence, burden, and topographic distribution of rpeHRF, as well as association with functional parameters, were determined. Fifty-six normal aged (33 female, mean age 68.1 ± 6.4 years), 34 eAMD (27 female, 71.7 ± 6.4 years), and 583 iAMD eyes (387 female, 72.0 ± 7.0 years) were included. rpeHRF counts were 0.16 ± 0.85 in normals, 0.33 ± 0.96 in eAMD, and 1.61 ± 2.49 in iAMD (P < .001). BCVA, LLVA, CS (all P < .001), and scPSD (P = .001) differed between disease groups, whereas RMDA and mesPSD did not. In iAMD, eyes with rpeHRF showed worse BCVA, LLVA, CS, scPSD (all P < .001), and mesPSD (P = .02). rpeHRF was found to be associated modestly with only CS, scPSD, LLVA, and BCVA. Presence and burden of rpeHRF were independently associated with impaired visual function and may thus serve as a prognostic biomarker for disease progression and enrichment criterion for future interventional trials.

Variability and extreme conditions within the Earth system are major drivers of adverse population-level health outcomes. To better understand how these risks may evolve under future climate change, outputs from Earth System Models (ESMs) are increasingly integrated into research within the field of Planetary Health. This study builds on a systematic literature review that assessed the current state of ESM usage in planetary health research and extends it by examining two cross-cutting aspects that emerged as particularly underexplored.The first aspect concerns how errors are handled between the two disciplines and which complications arise. Since in the majority of the studies reviewed the results were presented without a formal error analysis, we sought to identify the challenges of error propagation from the ESM over to the health model component and how uncertainties may be accounted for in different ways across studies. The results of this analysis show that the methodologies employed across different scientific disciplines vary in their treatment, quantification, and presentation of uncertainties. However, a proper error analysis is crucial for the credibility of scientific work, especially when communicating the results to a broad, including an non-academic, audience. Since climate change and its projected risks are already a highly politicized issue, particular care is required to not generate false assumptions.As a second focus, the study investigates whether and how vulnerable groups are accounted for in climate-related health projections. Because of growing evidence that climate-sensitive parameters such as heat stress or apparent temperature affect different genders or ages in distinct ways, we examined the extent to which these aspects are considered in the reviewed literature and whether ESM-derived climatic outputs are used as inputs for health models representing diverse population groups. Inspecting the set of research papers showed that only a few even mentioned words like “gender/sex” or even “vulnerability” of different groups. The word “women” was not found at all. Health risk projections that do not account for gender and other population subgroups, such as children, women and older adults, may systematically over- or underestimate climate change-related risks.Overall this study highlights the need for good and close collaboration and communication between scientific disciplines to guarantee reliable and unambiguous publications.