Universitätsklinikum Aachen

Smartphone-based first responder alert systems are akey component of the chain of survival in out-of-hospital cardiac arrest. In Germany, there are considerable regional differences in terms of qualification requirements and registration and approval processes. The impact of these barriers to access on the number of registered first responders has not yet been systematically investigated. Aretrospective secondary data analysis was performed based on freely available data. Ninety-nine regions with complete information on registration procedures, qualification requirements, and the number of registered first responders were included. In addition, the effect of voluntary 2 h short training courses on chest compressions on the subjective confidence of participants was examined in the Rheinisch-Bergisch district using asurvey. At the time of data collection, asmartphone-based first responder alert system had been implemented in 45% of emergency medical service areas. The average registration rate was 0.246% of the population. Regions with self-registration procedures had significantly higher registration rates than regions with formal registration (0.267% vs. 0.152%; p < 0.001). In two regions with self-declaration only and no verification of proof, rates of up to 0.489% were achieved. In the local case study, 2217 first responders were registered, 40% of whom had first aid qualifications only. The short training course was associated with asignificant increase in subjective safety. Low-threshold registration procedures are associated with higher registration rates in smartphone-based first responder alert systems. Accompanying short training courses can apparently increase the subjective confidence of first responders. Reducing formal barriers to access could help improve the availability of volunteer first responders. However, the effects of lower barriers to access on the psychological stress of first responders and on patient outcomes are unclear.

The updated version of the German S3 guideline for bladder cancer introduces several changes in the areas of diagnostics, perioperative systemic therapy, and rehabilitation, as well as psycho-oncological and palliative care for bladder cancer patients. In urinary diagnostics, the Paris system, including aquality algorithm, has been introduced to improve the comparability of cytological findings. Imaging diagnostics now recommends multiparametric magnetic resonance imaging (MRI) with Vesical Imaging-Reporting and Data System (VI-RADS) reporting as an alternative or complement to computed tomography (CT) scans. CT urography remains the gold standard for the upper urinary tract, while intravenous pyelography (IVP) is no longer recommended. In perioperative systemic therapy, the importance of multidisciplinary case conferences for muscle-invasive bladder cancer (MIBC) is emphasized to enable as many patients as possible to receive perioperative systemic therapy. Rehabilitation now follows quality criteria (multiprofessional teams, long-term concepts) and includes an expanded assessment of physical and psychological burdens. Particularly relevant is the treatment of sexual dysfunction in women after cystectomy. In psycho-oncology and palliative medicine, early integration of the S3 guidelines is required, including advanced care planning (ACP) starting from the diagnosis of advanced tumors. These changes aim for higher diagnostic accuracy, better treatment planning, and holistic patient care.

Monitoring of unfractionated heparin (UFH) in critically ill patients is challenging due to disease-related alterations of the coagulation system, directly affecting conventional laboratory tests, including activated partial thromboplastin time (aPTT). Measurement of anti-factor Xa activity (Anti-Xa) as an alternative to aPTT often lacks 24/7 availability. Whole blood viscoelastic testing (VET) may provide a feasible point-of-care alternative to guide UFH dosing in this setting. Additionally, VET is readily available in the environment found in our clinic, The aim of this study was to evaluate the diagnostic performance of viscoelastic testing compared with activated partial thromboplastin time for monitoring unfractionated heparin in critically ill patients and to define clinically applicable viscoelastic thresholds using anti-factor Xa activity as the reference standard. In this prospective observational study for UFH monitoring Anti-Xa, aPTT, and the VET clotting time IN/HI ratio (ClotPro®; Haemonetics, Boston, MA, USA) were determined in simultaneously taken blood samples. Anti-Xa results were used as the reference standard to categorize ongoing UFH anticoagulation intensity into four categories (prophylactic, sub-therapeutic, therapeutic, and overdosed). Diagnostic performance of aPTT and CT IN/HI ratio were evaluated against Anti-Xa using ROC analysis and Cohen’s Kappa. Test performance was evaluated using ROC analysis, multiclass classification, and weighted Cohen’s kappa. Between September 2020 and July 2022, 466 datasets from 75 ICU patients receiving intravenous UFH were analyzed. Compared to aPTT, AUC values for CT IN/HI were higher for detecting prophylactic (0.817 vs. 0.726), therapeutic (0.690 vs. 0.494) and overdosed (0.845 vs. 0.708) UFH levels. Thresholds of > 1.4, > 1.9, and > 2.3 for the CT IN/HI ratio corresponded to sub-therapeutic, therapeutic, and overdosed ranges, respectively. The CT IN/HI ratio showed moderate agreement with Anti-Xa classification (κ = 0.450), while aPTT agreement was insufficient (κ = 0.220). The CT IN/HI ratio offers a reliable point-of-care alternative to standard UFH monitoring, in the case it is readily available. It provides better alignment with Anti-Xa activity than aPTT and may improve anticoagulation management in critically ill patients, especially when Anti-Xa testing is delayed or unavailable. DRKS-ID DRKS00028689 (https://drks.de/search/de), PI: Lars Heubner, retrospectively registered 30.03.2022.

Colorectal cancer (CRC) exhibits increased levels of arachidonic acid-derived pro-inflammatory derivatives indicating an uptake of dietary polyunsaturated fatty acids (PUFAs). We aimed to investigate uptake of extrinsic fatty acids (FAs) in tumours and their relevance for CRC lipid metabolism and progression. Total FAs were quantified using gas chromatography-mass spectrometry in non-diseased mucosa and tumour tissue from patients with CRC of a discovery cohort (n=152), validated in an independent cohort (n=28) and associated with clinical, genomic and microbiome data. The genetic mouse tumour model Apc1638N was used to track the flux of stable isotope-labelled FAs in tumours from the intestinal lumen. The relationship between FA uptake and tumour progression was investigated in 2D and 3D cell models. Extrinsic long chain PUFAs, including arachidonic acid, accumulate in CRC, particularly in right-sided tumours, and in tumours of Apc1638N mice. The CRC-specific FA profiles were independent of sex, molecular subtypes, early-disease or late-disease onset. The absorption of FAs from the intestinal lumen in tumours was confirmed in specific pathogen-free Apc1638N mice. In the absence of the microbiome, in germ-free Apc1638N mice, fewer tumours were developed, and survival was increased. Inhibition of FA import or β-oxidation reduces cancer cell proliferation. Extrinsic FAs accumulate in CRC, verifying a central role of arachidonic acid-derived inflammatory mediators, but also suggesting a relevance of dietary FAs for cancer cell proliferation. It will be intriguing to explore to what extent targeting this flux pathway together with the interrelated microbiome opens new therapeutic avenues for CRC in humans.

Selection of the optimal recipient artery in superficial temporal artery to middle cerebral artery (STA-MCA) extracranial-intracranial bypass surgery is essential to ensure adequate cerebral perfusion. Various pre- and intraoperative tools for target vessel selection have been proposed. Indocyanine green fluorescence video angiography (ICG-VA) enables real-time visualization of cerebral hemodynamics, facilitating recipient vessel selection and anastomotic evaluation. Here, we review the literature and present the use of qualitative ICG-VA to support intraoperative decision-making during double-barrel (DB) STA-MCA bypass surgery. We report the case of a 68-year-old patient with bilateral steno-occlusive cerebrovascular disease, who developed progressive hemodynamic compromise of the left hemisphere after prior right-sided STA-MCA bypass. Preoperative imaging demonstrated impaired perfusion and posterior-to-anterior leptomeningeal collateralization from the posterior cerebral artery. During the left-sided DB bypass surgery, intravenous ICG-VA was used to assess relative cortical perfusion. Two superficial M4 branches with the most pronounced perfusion delay were selected as recipients based on the ICG-VA and anatomical criteria. Postoperative angiography confirmed graft patency. At short-term follow-up, the patient remained neurologically stable, with complete regression of preoperative symptoms. This case illustrates the application of qualitative ICG-VA for perfusion-oriented recipient vessel selection in DB STA-MCA bypass for steno-occlusive disease. Real-time perfusion assessment may complement conventional anatomical criteria for recipient vessel selection in flow-augmentation procedures. Further studies incorporating quantitative hemodynamic analysis are warranted.

370 Background: Locally-advanced, inoperable T4 prostate cancer (PCa) is a challenging scenario usually treated by combined systemic treatment and/or radiotherapy. To date, no prospective trial examining inductive hormonal therapy to achieve operability in such patients exists. Retrospective data demonstrated successful treatment with radical prostatectomy at PSA nadir. While only a minority of these patients was cured, long-term survival with persistent sensitivity to androgen deprivation therapy (ADT) was observed in the majority. The INDUCTA trial aimed to prospectively investigate whether combined inductive treatment with ADT and Apalutamide reliably induces operability in T4 PCa. Methods: INDUCTA enrolled patients with cT4 PCa, considered inoperable (confirmed by DRE and mpMRI) with no prior radio- or antihormonal therapy and without metastases in conventional imaging (CT and bone scan). After 6 months of ADT and Apalutamide 240 mg daily, local disease stage and operability were reassessed. If operable, patients received robot-assisted radical prostatectomy (RARP). We report the proportion of patients achieving operability after combined inductive therapy (primary endpoint), together with peri- and early postoperative results. Results: Of 27 patients screened, 21 (mean age 69.4±7.2 yrs) entered the trial and completed treatment (compliance 96.8%). At diagnosis, median PSA was 47.4 ng/mL (5.4-395). Operability was confirmed in all 21 after inductive therapy. Median PSA nadir after ADT was 0.05 ng/mL (0.01-1.32). While one operable patient did not undergo surgery due to cardiac deterioration, RARP was performed in 20 patients. There were no rectal injuries and no grade IV or V complications, while grade III occurred in only two cases. Table 1 illustrates the perioperative parameters and final RARP pathology. Quality of life (FACT-G, FACT-P,EQ-5D-3L) showed no baseline deterioration. Conclusions: Inductive therapy with ADT and Apalutamide leads to essential downstaging enabling RARP in 100% of patients. These results set the stage for a new standard of care treatment concept for T4 PCa. Besides disease control preventing future complications, removal of the locally advanced primary tumor should positively influence the further course of disease and even give those affected a chance to be cured. Clinical trial information: 2021-003523-16. Perioperative and pathological parameters. Total, N = 20 Duration of surgery [min, median (range)] 163 (106 - 244) Blood loss [mL, median (range)] 175 (30 - 800) Duration of hospitalization [days, median (range)] 7 (3 - 53) Catheter: days in situ [median (range)] 5 (3 – 93) n % Pathological T stage pT2c 1 5 pT3a 7 35 pT3b 12 60 Pathological evaluation of regional lymph nodes pN0 9 45 pN1 11 55 Surgical margin status negative 13 65 positive 7 35