Jena University Hospital

Electronic alert systems (e-alerts) based on blood creatinine changes are used to detect acute kidney injury (AKI) in hospitalized patients. While most e-alerts follow the KDIGO (Kidney Disease: Improving Global Outcomes) definition for AKI, the Association for Diagnostics & Laboratory Medicine (ADLM, formerly AACC) has proposed alternative AACC criteria. This study directly compares e-alerts using both AKI definitions in relation to in-hospital outcomes. E-alerts based on KDIGO and AACC criteria were retrospectively assessed over 1 year in hospitalized patients at a tertiary care hospital. Adverse outcomes included in-hospital death, initiation of dialysis, and renal function decline at hospital discharge according to acute kidney disease criteria. Among 14 719 patients, 1304 had adverse outcomes. KDIGO-based e-alerts were fired in 2598 patients of whom 2554 also met AACC criteria, 1138 were detected by AACC-based e-alert alone. AACC-based alerts were more sensitive (81.4% vs 74.0%) but less specific (80.4% vs 87.8%) for the composite adverse outcome. KDIGO but not AACC-based e-alerts showed reduced sensitivity in female patients and patients without chronic kidney disease. AACC-based alerts triggered earlier than KDIGO-based e-alerts in 22% of dual-alert cases. This subgroup had a higher rate of adverse outcomes (42.7%) than those with e-alerts firing simultaneously (35.1%). AACC-based e-alerts improve early AKI detection and reduce bias, potentially enhancing risk stratification. However, they also increase alert burden. These findings provide a basis for future prospective comparative studies.

The aim of this study was to investigate the dynamic biodistribution of [68Ga]Ga-TEoS-DAZA, a functional liver PET tracer, in 2 preclinical models (ostrich embryos and mice) and in a healthy human liver donor to identify similarities and differences among the 3 species, which are relevant in translational nuclear medicine. Furthermore, the molecular pathway and metabolism of [68Ga]Ga-TEoS-DAZA was investigated. Methods: The dynamic biodistribution of [68Ga]Ga-TEoS-DAZA was determined via PET/CT in ostrich embryos, in healthy mice (C57BL/6), and in a healthy human liver donor. Hepatocyte transporter binding studies were performed in transfected HEK293t cells. Metabolite analysis was performed in samples from ostrich embryos and a healthy liver donor. Blocking studies against cyclosporine A were performed in ostrich embryos. Results: The biodistribution of [68Ga]Ga-TEoS-DAZA was comparable in ostrich embryos, healthy mice (C57BL/6), and the healthy donor. In all 3 species, the tracer showed specific uptake in liver tissue (30-40 %IA at time of peak) and subsequent biliary excretion, whereas less than 5 %IA activity was excreted renally. The hepatic transit time in mice was significantly faster than in ostrich embryos and human, with mice exhibiting a much shorter time-to-peak (1.7 min) than the other 2 species (15-21 min) and rapid clearance of the tracer from the liver into the intestines. [68Ga]Ga-TEoS-DAZA is a substrate for OATP1B3, with tracer uptake into the liver being hampered in the presence of cyclosporine A. Tissue samples revealed an as yet unknown radiometabolite of [68Ga]Ga-TEoS-DAZA, indicating hepatic metabolism. Conclusion: [68Ga]Ga-TEoS-DAZA was shown to be a suitable hepatobiliary tracer using both mice and ostrich embryos as preclinical models; however, there were limits in translatability in both models because of a distinctly faster hepatic uptake and biliary excretion (mice) or a slower biliary excretion (ostrich embryo) compared with that in the human.

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.

Transoral laser microsurgery (TOLMS) is an established organ-preserving treatment for early-stage and selected intermediate-stage laryngeal squamous cell carcinoma (SCC). Initially indicated for Tis-T1 lesions, its use has progressively expanded to carefully selected T2 and T3 tumors, providing oncologic outcomes comparable to open surgery and (chemo)radiotherapy [(C)RT] while offering favorable functional results. The CO₂ (carbon dioxide) laser is the preferred device for TOLMS due to its precision and minimal thermal injury, allowing accurate tumor resection with optimal margin control. Successful application of TOLMS relies on strict patient selection and comprehensive pre- and intraoperative assessment. High-definition videolaryngoscopy, angled telescopes, bioendoscopic techniques, advanced imaging modalities, and emerging artificial intelligence tools have significantly improved the evaluation of tumor extent, biological behavior, and laryngeal function. Adequate laryngeal exposure is a critical prerequisite, as difficult exposure is associated with higher rates of positive margins and inferior oncological outcomes. Preoperative imaging, particularly magnetic resonance imaging (MRI) and dual-energy computed tomography (CT), is essential for assessing deep tumor extension, cartilage invasion, and involvement of key anatomical subsites, including the anterior commissure (AC), paraglottic space (PGS), and pre-epiglottic space (PES). AC involvement alone is not an absolute contraindication to TOLMS; however, vertical trans-AC extension and posterior PGS invasion, especially when associated with arytenoid fixation, represent major limitations due to the difficulty in achieving adequate oncologic margins. Surgical margin assessment remains challenging because of specimen shrinkage and variability in pathological evaluation, yet positive margins-particularly deep or multiple-are associated with worse disease-specific survival and laryngeal preservation. In supraglottic SCC, TOLMS is feasible for T1-T2 and selected T3 tumors, although functional outcomes decline with increasing extent of resection and patient age. The role of TOLMS in the salvage setting is limited and requires highly selective indications. In conclusion, TOLMS is an effective treatment for appropriately selected laryngeal cancers, provided that meticulous diagnostic work-up, surgical expertise, and multidisciplinary decision-making are ensured.

Abstract The ability to detect host cell factors during Staphylococcus aureus infection in vitro by immunofluorescence microscopy is severely hampered by staphylococcal protein A (SpA), a cell wall-anchored protein that binds the fragment crystallizable (Fc) region of immunoglobulins. This interaction generates strong nonspecific fluorescent signals on the bacterial surface, complicating data interpretation and limiting the accuracy of quantitative image analysis. Several measures have been put forward to overcome this obstacle, most importantly the pre-incubation with an anti-SpA antibody (αSpA) and the use of human serum (HS) as blocking agent and antibody diluent. To highlight this feature to general fluorescence microscopy users, we here systematically evaluated these two strategies. Using S. aureus coated on coverslips and S. aureus -infected A549 cells, we highlight the efficiencies of both approaches to markedly reduce nonspecific fluorescence, with HS treatment yielding the most profound suppression. Notably, HS, containing high levels of human immunoglobulins, offered a robust, cost-effective and broadly applicable solution for minimizing SpA-driven artifacts, thereby improving immunofluorescence microscopy in S. aureus infection models in vitro .

In this contribution, we aim at assessing the detectability of atmospheric water vapor uptake by dry soils at a variety of spatial scales and methodologies, from the ecosystem scale via eddy covariance, through larger scales via earth system models, and gridded products. Water vapor fluxes in the soil and at the soil-atmosphere interface are driven by vapor concentration gradients. Until today, it is mostly assumed that the soil pore air is roughly at 100% relative humidity (RH), resulting in vapor fluxes that are almost always towards the atmosphere. However, the vapor state in soil pore air is linked to the soil water (matric) potential. As the water potential becomes more negative, the equilibrium RH within the soil decreases substantially. Under these conditions, the soil behaves like a ‘thirsty material’: when the atmospheric vapor pressure exceeds that of the soil pores, vapor is adsorbed onto the solid soil particle surfaces, and the net vapor flux is directed towards the soil. Using subdaily measurement data from a globally distributed network of eddy covariance stations, we show an emergent functional relationship between volumetric water content (VWC), RH, and latent heat (λE) flux direction at the ecosystem scale. Vapor fluxes towards the soil under dry conditions can be explained by the soil's sorptive forces inducing very low water potentials. Based on eddy covariance data, we find that soil vapor adsorption most frequently occurred in arid and semi-arid regions, particularly in ecosystems with sparse vegetation such as savannas and dry shrublands. On average, soil vapor adsorption occurs for 4 ± 1.1 hours per night, and may last up to 7 hours and on more than 150 nights per year in some drylands.Furthermore, we demonstrate that the relationship between VWC, RH, and the vapor flux direction is evident in a wide range of in situ measurements in drylands, including lysimeter and humidity profile data. However, this relationship is absent in site-level runs of gridded observation-based data products and land surface models.We demonstrate for the first time that the effect of adsorptive forces can be detected at the ecosystem scale, several meters above the ground. Our findings at the operating scale of flux towers can be used to evaluate and improve model representation of land-atmosphere exchange in dry conditions. Additionally, the results highlight the influence of sorptive forces on sub-daily soil-atmosphere interactions, particularly in sparsely vegetated drylands.

Health services research faces the challenge of providing sound recommendations for action for the further development of health systems and care. The application of causal inference methods offers health services researchers an excellent opportunity to identify causal relationships under everyday conditions. The role of clinical trials with a classic randomised controlled trial (RCT) design is recognised as suitable for gaining insights that help establish causal inference, but other methodological approaches to generating evidence also play an important role in health services research.The discussion paper presents key concepts and assumptions of causal inference and highlights their relevance for health services research. The paper makes it clear that in order to fulfil the assumptions, it is necessary to integrate theory, contextual knowledge, understanding of mechanisms and formal concepts, such as directed acyclic graphs (DAGs), into a suitable empirical study design. To this end, RCTs, quasi-experimental methods, causal machine learning, target trial emulation, in silico trials and the mixed-methods approach of integrated inference are presented and discussed in terms of their applicability in health services research and their internal and external validity.All of the approaches presented here can contribute to the estimation of causal effects when used in a targeted manner and in accordance with the central assumptions. Their suitability depends largely on the research question, data quality, theoretical modelling and contextual knowledge. The combination of complementary designs and high quality data sources can increase the robustness of causal conclusions.Causal inference in health services research is not only a methodological procedure, but an integrative process that systematically combines theory, methodology and contextual knowledge. By consistently linking these aspects, health services research can generate differentiated and actionable insights that go beyond correlative analyses and enable an understanding of the mechanisms of causal processes. This can lead, for example, to evidence-supported recommendations that critically examine the often non-evidence-based status quo and reliably evaluate the benefits of new models.