Universitätsklinikum Erlangen

The 2024 European Society of Cardiology (ESC) guidelines on chronic coronary syndrome comprehensively summarize the symptoms, diagnostics and treatment of coronary artery disease, excluding acute coronary syndromes. The processing always begins with an estimation of the clinical probability, which should include not only the symptom profile but also the number of cardiovascular risk factors and is further modified by any conspicuous findings in electrocardiography (ECG), exercise testing, or echocardiography. For further diagnostics, coronary angiography via computed tomography is the first-line approach if the probability lies between 5% and 50%. For probabilities of 50–85% procedures for imaging-based ischemia detection are indicated, while for even higher probabilities immediate invasive diagnostics are given priority. The treatment includes intensive risk modification, medicinal anti-anginal treatment and finally revascularization by coronary intervention or bypass surgery. In the absence of high-risk constellations a medication-based approach should be initially preferred, with revascularization indicated if symptoms persist. The new guidelines also extensively address angina and ischemia without obstructive coronary lesions. In this context, intensive risk modification and initial medication treatment are again recommended.

Sclerosing epithelioid fibrosarcoma (SEF) was originally described as a peculiar variant of fibrosarcoma in 1995. Subsequent studies showed that conventional SEF was associated with both immunohistochemical expression of MUC4 and EWSR1/FUS gene rearrangements with CREB3L1 as the predominant fusion partner. Since then, a distinct group of fibrous tumors characterized by YAP1::KMT2A and KMT2A::YAP1 gene rearrangements and SEF-like morphology has been described. These YAP1::KMT2A-rearranged sarcomas were further shown to lack both immunohistochemical expression of MUC4 and canonical EWSR1/FUS gene rearrangements. To better understand whether the YAP1::KMT2A-rearranged sarcomas represent a subset of MUC4-negative SEF or a distinct entity, we studied 22 cases of YAP1::KMT2A-rearranged sarcomas, the largest series to date, and performed a literature review of all previously reported next-generation sequencing (NGS)-confirmed cases. These sarcomas often arose in young adults with a median age of 38 years and a male to female (M:F) ratio of 1.4:1. They predominantly involved somatic soft tissue; however, we report the first case of a tumor that primarily developed inside bone. Immunohistochemical studies showed that the tumors often demonstrated expression of YAP1 and EMA, while all tested cases were negative for MUC4. NGS confirmed the presence of YAP1::KMT2A gene fusions in all cases, some of which initially had false negative results with targeted FISH and solid tumor panel testing. Clinical follow-up information was available in 14 patients with a median follow-up of 25 months (range 1 to 170 months). Local recurrence occurred in three patients (21%) and metastasis developed in seven patients (50%). DNA methylation analysis further showed that YAP1::KMT2A-rearranged sarcomas formed a distinct cluster, which was clearly separate from both conventional SEF and low-grade fibromyxoid sarcoma (LGFMS). These results suggest that YAP1::KMT2A-rearranged sarcomas likely represent a unique sarcoma subtype with propensity for aggressive behavior.

In recent years, various magnetic resonance (MRI) and positron emission tomography (PET) parameters have been investigated in breast cancer. Parametric imaging focuses on the visualization and quantification of biological, physiological, and pathological processes at the cellular and molecular level. It therefore provides important insights into the key processes in carcinogenesis and tumor progression. This article aims to illustrate the importance for the management of breast cancer. Based on the current literature, an overview of the current state of parametric breast imaging and its importance in therapy management is given. Moreover, future opportunities and challenges are highlighted. Parametric imaging in breast cancer includes MRI, nuclear medicine procedures such as PET, the combination of different techniques (PET-CT, PET-MRI) and the use of specific radiotracers. Parametric MRI of the breast mainly uses T2 and diffusion-weighted imaging (DWI) as well as dynamic contrast-enhanced MRI (CM-MRI). Quantitative and qualitative imaging biomarkers provide insights into tumor biology and allow conclusions to be drawn about the molecular subtype or prognosis. Recently, parametric imaging has become established in breast diagnostics. It is constantly evolving and will continue to gain in importance in the forthcoming years. It offers the opportunity to improve the diagnosis and treatment management of breast cancer.

Objective Oral antitumour therapeutics (OAT) are increasingly used due to improvements in outcomes and their convenient application. However, complex intake regimens pose several challenges. The randomised AMBORA trial (Medication Safety With Oral Antitumour Drugs) demonstrated highly positive outcomes of a clinical pharmacological/pharmaceutical care program for adults treated with numerous OAT, but comparable concepts in paediatrics are lacking so far. Methods We used a parallel mixed-methods approach to develop a tailored pharmacological/pharmaceutical care program for OAT in paediatrics (youngAMBORA). We combined a quantitative analysis of tumour entities and used OAT in a paediatric cancer centre with a qualitative survey for patients, caregivers, and healthcare professionals to identify particular demands and educational needs (e.g., application problems, side effects). Results Leukaemia (77/315) and antimetabolites (95/151) were the most frequently observed entity and OAT, respectively. Of 22 surveyed patients, 81.8% wanted to be involved in oral medication education. Compared to caregivers, significantly more healthcare professionals graded the three most common application problems to be challenging (‘Smell/taste’: 32/36 vs. 23/42, p = 0.001; ‘Refusal of intake’: 31/36 vs. 16/42, p<0.001; ‘Swallowing problems’: 28/36 vs. 21/42, p = 0.011). We identified nine relevant side effects, of which two (‘Skin dryness’, ‘Taste changes’) were not included in 15 previously published core side effects of the Common Terminology Criteria of Adverse Events (CTCAE) item library. Conclusion Based on the present findings, the tailored youngAMBORA care program will include: 1) counselling sessions for classic and targeted OAT, 2) child-friendly support with drug application, and 3) systematic evaluation of 17 relevant side effects from patients’ and caregivers’ points of view including age-appropriate information material.

AI tools in radiology are revolutionising the diagnosis, evaluation, and management of patients. However, there is a major gap between the large number of developed AI tools and those translated into daily clinical practice, which can be primarily attributed to limited usefulness and trust in current AI tools. Instead of technically driven development, little effort has been put into value-based development to ensure AI tools will have a clinically relevant impact on patient care. An iterative comprehensive value evaluation process covering the complete AI tool lifecycle should be part of radiology AI development. For value assessment of health technologies, health technology assessment (HTA) is an extensively used and comprehensive method. While most aspects of value covered by HTA apply to radiology AI, additional aspects, including transparency, explainability, and robustness, are unique to radiology AI and crucial in its value assessment. Additionally, value assessment should already be included early in the design stage to determine the potential impact and subsequent requirements of the AI tool. Such early assessment should be systematic, transparent, and practical to ensure all stakeholders and value aspects are considered. Hence, early value-based development by incorporating early HTA will lead to more valuable AI tools and thus facilitate translation to clinical practice. Clinical relevance statement This paper advocates for the use of early value-based assessments. These assessments promote a comprehensive evaluation on how an AI tool in development can provide value in clinical practice and thus help improve the quality of these tools and the clinical process they support. Key Points Value in radiology AI should be perceived as a comprehensive term including health technology assessment domains and AI-specific domains. Incorporation of an early health technology assessment for radiology AI during development will lead to more valuable radiology AI tools. Comprehensive and transparent value assessment of radiology AI tools is essential for their widespread adoption.

Given the high prevalence of artificial intelligence (AI) research in medicine, the development of deep learning (DL) algorithms based on image recognition, such as the analysis of bone marrow aspirate (BMA) smears, is rapidly increasing in the field of hematology and oncology. The models are trained to identify the optimal regions of the BMA smear for differential cell count and subsequently detect and classify a number of cell types, which can ultimately be utilized for diagnostic purposes. Moreover, AI is capable of identifying genetic mutations phenotypically. This pipeline has the potential to offer an accurate and rapid preliminary analysis of the bone marrow in the clinical routine. However, the intrinsic complexity of hematological diseases presents several challenges for the automatic morphological assessment. To ensure general applicability across multiple medical centers and to deliver high accuracy on prospective clinical data, AI models would require highly heterogeneous training datasets. This review presents a systematic analysis of models for cell classification and detection of hematological malignancies published in the last 5 years (2019–2024). It provides insight into the challenges and opportunities of these DL‐assisted tasks.

TiO2 nanotubes flow through membranes (TNTsM) were fabricated via anodization of Ti foil and explored as a biosensing platform for creatinine detection. The electrodes were prepared in different configurations including...

We analyze theoretically several dynamical scenarios of irradiation in molecules and clusters. We focus on fast and Ultrafast (UF) processes as attained in various laser setups. We consider both simple laser pulses and pump-and-probe combinations. We explore various such combinations with different frequencies and durations. The basic theory is Time-Dependent Density-Functional Theory (TDDFT) used at the simplest Local Density Approximation (LDA) level together with a simple and robust self-interaction correction. The TDLDA can be complemented by a Relaxation Time Ansatz which accounts for incoherent correlations beyond effective mean field. We explore fast and ultrafast processes starting in the femtosecond range. We next consider several pump-and-probe setups mixing IR and XUV pulses, the latter one possibly delivered within an atto train. We finally explore UF irradiation in the XUV domain leading to creation of deep lying vacancies. Such setups lead to an unexpected response which is analyzed.

Purpose Transferring adult cancer patients from the hospital to the home environment for home parenteral nutrition (HPN) can be challenging. There is limited real-world data on how those affected perceive this situation. Our aim was to assess the quality of life (QoL) on HPN and the benefits and burdens from the cancer patient's perspective. Methods This observational study from Germany examined the QoL on HPN on the basis of the Functional Assessment of Cancer Therapy – G questionnaire (FACT-G). The benefits and burdens of HPN were assessed using predefined questions and answers tailored to the situation of this patient group. Results 139 adults with advanced solid tumors in a palliative setting at 10 hospitals in Germany were eligible for the study. The follow-up was 12 weeks. At week 4, the Least-square (LS) mean (95% CI) change from baseline in the total FACT-G score was 0.9 (-2.4; 4.2) points, indicating QoL stability. HPN was associated with few complications, with a low rate of hospital readmission due to catheter-related issues (3.8%; n = 5). In the patient assessment of the benefits of HPN, the LS mean values at Week 4 ranged between 7.6 and 8.5 on a 10-point Likert scale. The most commonly perceived burden was "restricted mobility". Conclusion With thorough preparation for home parenteral nutrition, the transition from hospital to home care environment works well. QoL is largely maintained through HPN, and cancer patients perceive this situation as not or minimally burdensome alongside their underlying disease, although many patients found the limited mobility to be a burden. Trial Registration number NCT03425435 / Date of registration: February 01, 2018.

Intracerebral hemorrhage (ICH) is a medical emergency with high morbidity and mortality. General and specific therapeutic approaches aim to improve the patient’s outcome. The objective of this article is to present the current scientific state regarding the in-hospital care of patients with ICH. This narrative review presents and analyzes the current evidence regarding treatment options for ICH. The primary focus of acute therapy is to prevent the prognostically unfavorable enlargement of the hematoma. This is associated with specific computed tomographic markers, as well as the initial hematoma volume, the use of anticoagulants, and a shorter time from symptom onset. An elevated blood pressure should be promptly and precisely lowered to a systolic value below 140 mm Hg, and the inhibition of coagulation must be immediately antagonized. This should be constituted into a treatment bundle with optimal adjustment of vital parameters and implementation of basic intensive care measures. Intraventricular hemorrhage can be effectively treated by external ventricular drainage and intraventricular fibrinolysis, with or without additional lumbar drainage. Minimally invasive procedures for hematoma removal have the potential to improve outcomes in lobar ICH. A realistic prognostic assessment forms the basis for informed treatment decisions regarding ICH. In recent years, the evidence supporting aggressive therapeutic approaches in ICH has become increasingly robust, with reliable results now available regarding the efficacy of individual or combined measures.

Zusammenfassung Eine wichtige Voraussetzung für die Sicherung einer rationalen Antibiotika-Verordnung ist die Verfügbarkeit und Prüfung von Verbrauchsdaten. Wir haben erstmals vor 10 Jahren solche Daten für Akutkrankenhäuser in Deutschland vorgestellt und möchten die Entwicklungen seither beschreiben. Die jährlichen Antibiotika-Verordnungsmengen aus Akutkrankenhäusern wurden für den Zeitraum 2012/13 bis 2021/22 analysiert, dargestellt als Tagesdosen pro 100 Pflegetage, wobei die Tagesdosis-Definition speziell für den Krankenhausbereich adaptiert wurde („recommended daily dose“, RDD). Zusätzlich wurde eine Hochrechnung auf die Gesamtbevölkerung unter Verwendung der seitens der WHO definierten Tagesdosen („defined daily doses“, DDD) vorgenommen. Die Antibiotika-Verbrauchsdichte in deutschen Akutkrankenhäusern ist im betrachteten 10-Jahres-Zeitraum nicht angestiegen. Sie betrug im Median im Jahre 2012/13 insgesamt 41,9 RDD/100 Pflegetage (n=169, Interquartilbereich 35–48 RDD/100) im Vergleich zu 42,1 RDD/100 im Jahre 2021/22 (n=329, Interquartilbereich 35–48 RDD/100). Auf die Bevölkerung bezogen lag der Verbrauch 2021/22 bei 1,85 DDD pro 1000 Bewohner und Tag. Die Verbrauchsdichte war in Universitätskliniken (54,0 RDD/100) signifikant höher als in den nicht universitären Krankenhäusern unterschiedlicher Größe, deren Verbrauchswerte sich nur wenig unterschieden (Mediane 39,8–44,0 RDD/100). Penicilline wurden zunehmend häufiger (Anstieg des Anteils an allen Wirkstoffen +63%), Fluorchinolone (– 54%) und Cephalosporine der ersten und zweiten Generation (– 41%) seltener eingesetzt. Auf Intensivstationen war die Verordnungsdichte rund doppelt so hoch wie auf den Normalstationen. Hohe Verordnungsdichten wurden auch in universitären hämatologisch-onkologischen Abteilungen (Median 96,8 RDD/100) und in Fachabteilungen für Urologie (Mediane 65,1–70,5 RDD/100) und HNO-Heilkunde (Mediane 49,1–60,9 RDD/100) beobachtet. Bei gleichbleibender Antibiotika-Verordnungsdichte im Krankenhaus insgesamt gab es Verschiebungen im Spektrum der Wirkstoffgruppen, mit einer zunehmenden Bevorzugung von Penicillin-Derivaten. Auf die Bevölkerung hochgerechnet lag der Verbrauch leicht oberhalb des europäischen Durchschnitts.

Background Objective Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication in craniotomy patients and is associated with increased morbidity and mortality. The duration of surgery is a known risk factor. Other factors such as positioning and tumor entity have hardly been investigated or are controversial. In two pilot studies, the determination of plasma D-dimer concentration led to a high detection rate of DVT, while the use of intermittent pneumatic venous compression (IPC) drastically reduced the incidence of VTE. In the present study we investigated the efficacy of the two approaches, either alone or in combination, in a large patient cohort. Methods 1759 patients who underwent elective craniotomy between 2009 and 2023 were retrospectively analyzed. The staggered use of D-dimer determination and intraoperative use of IPC resulted in 3 groups: Group 1: no procedure; Group 2: D-dimer evaluation; Group 3: IPC and D-dimer evaluation. If the D-dimer level was ≥ 2 mg/l (Fibrinogen equivalent units; FEU), venous ultrasound was performed. Age, gender, tumor entity, duration and extent of surgery, patient positioning, type of VTE were also recorded and analyzed. Results The introduction of postoperative D-dimer evaluation increased the rate of detection of thrombosis from 1.7% in group 1 to 22.6% in group 2. The addition of IPC reduced the rate of thrombosis to 4.4%. Age, gender and patient positioning did not affect the rate of VTE. We were able to confirm the duration of surgery as an individual risk factor and showed that WHO grade 4 tumors and metastasis have an increased VTE risk. Conclusions If D-Dimer levels are not analyzed routinely about 20% of craniotomy patients suffer from a clinically silent thrombosis. Each with the risk of fate PE. Intraoperative use of IPC during craniotomy dramatically reduces the risk of VTE.

Imaging molecular processes associated with inflammatory disease has been revolutionized by hybrid imaging using positron emission tomography/computed tomography (PET/CT). PET/CT visualizes metabolic activity as well as protein expression and provides a comprehensive whole-body evaluation. It has the potential to reveal inflammation prior to detection of structural changes in inflammatory joint diseases. FAP is a type II transmembrane glycoprotein overexpressed not only in the stroma of tumors but also in the fibrotic processes of certain immune-mediated disorders. The recent introduction of fibroblast activation protein inhibitors (FAPI) labeled by positron emitters and thus suitable for PET/CT allows to investigate FAP expression in vivo. This review will focus on the use of FAPI-PET/CT for the diagnosis and evaluation of treatment response in inflammatory joint diseases.