Hochschule Bremerhaven

Background Although systemic therapies have improved considerably over the last decade, up to 50% of patients with metastatic melanoma still die due to disease progression. Oncological treatment at the end-of-life phase is challenging. The aim of this study was to investigate the frequency and type of systemic therapy received by melanoma patients in their end-of-life phase. Methods Patients with metastatic melanoma who had died between January 1, 2018 and October 31, 2022 were identified from the prospective multicenter skin cancer registry ADOReg. Study endpoints were percentage of patients who had been treated with systemic therapy within the last three months of life, timepoint of initiation of the last-line therapy, overall survival, treatment benefit and the incidence of treatment-related adverse events. Results In total, 1067 patients from 46 skin cancer centers were included. Most of the patients (63%) had received immune checkpoint inhibitors (ICI) as last-line therapy, 22% targeted therapies (TT) and 12% chemotherapy (CTX). Comparing last-line ICI and TT, patients with TT were significantly more likely to benefit from treatment and had significantly fewer and milder treatment-related AE than patients with ICI. Even though two thirds of patients had received ICI as a last-line therapy, the majority of these patients (61%) had stopped therapy within the last 30 days of life, whereas the majority of patients with TT (66%) still continued their treatment to the end of life. We found markedly fewer patients with initiation of ICI within 30 days before their death (19%) compared to a historic cohort including patients who died in 2016 or 2017 (39%). Conclusion Treatment approaches near the end of life have markedly changed in skin cancer centers in Germany over recent years, with ICI prescribed less frequently in the end-of-life phase. In contrast, TT are frequently administered, even within the last 30 days of life. It should also be considered that discontinuation of TT can result in rapid tumor progression. Due to the oral administration and a low rate of severe toxicity, TT appear to be a suitable treatment option, even in the end-of-life situation of melanoma patients.

Coastal ecosystems are increasingly experiencing anthropogenic pressures such as climate warming, CO2 increase, metal and organic pollution, overfishing, and resource extraction. Some resulting stressors are more direct like pollution and fisheries, and others more indirect like ocean acidification, yet they jointly affect marine biota, communities, and entire ecosystems. While single-stressor effects have been widely investigated, the interactive effects of multiple stressors on ecosystems are less researched. In this study, we review the literature on multiple stressors and their interactive effects in coastal environments across organisms. We classify the interactions into three categories: synergistic, additive, and antagonistic. We found phytoplankton and bivalves to be the most studied taxonomic groups. Climate warming is identified as the most dominant stressor which, in combination, with other stressors such as ocean acidification, eutrophication, and metal pollution exacerbate adverse effects on physiological traits such as growth rate, fitness, basal respiration, and size. Phytoplankton appears to be most sensitive to interactions between warming, metal and nutrient pollution. In warm and nutrient-enriched environments, the presence of metals considerably affects the uptake of nutrients, and increases respiration costs and toxin production in phytoplankton. For bivalves, warming and low pH are the most lethal stressors. The combined effect of heat stress and ocean acidification leads to decreased growth rate, shell size, and acid-base regulation capacity in bivalves. However, for a holistic understanding of how coastal food webs will evolve with ongoing changes, we suggest more research on ecosystem-level responses. This can be achieved by combining in-situ observations from controlled environments (e.g. mesocosm experiments) with modelling approaches.

The present research explores theoretical and computational aspects of the morphological instability of Kirkendall voids induced by a directed flux of vacancies. A quantitative phase-field model is coupled with a multi-component diffusion model and CALPHAD-type thermodynamic and kinetic databases to obtain a meso-scale description of Kirkendall void morphologies under isothermal annealing. The material under investigation is a diffusion couple consisting of a multi-phase multi-component single-crystal Ni-based superalloy on one side and pure Ni on the other side. The flux of the fastest diffuser in the superalloy, Al, towards the pure Ni causes a strong flux of vacancies in the opposite direction. This directed flux of vacancies leads to morphologically instable growth of voids. Phase-field simulations are performed in two (2D) and three dimensions (3D) to understand these instabilities, and the results are compared with experimental observations obtained by synchrotron X-ray tomography. Finally, the simulation results are analyzed with respect to the Mullins–Sekerka linear stability criterion.

The placement of cardiovascular implantable electronic devices (CIED) comes with a risk of adverse events (AE). AE comprise complications associated with the procedure and the device. CIED infection is a severe AE. Reported CIED infection rates are regionally differing and publications of contemporary large cohort data regarding CIED infections for Germany are lacking. This investigation provides rates of CIED infection related hospital admission and CIED infection related mortality in Germany. Data from Germany’s largest healthcare insurance fund was screened for CIED procedures during the period: January to December 2015. These data included placement, revision with aim to up- or downgrade, generator substitution, early revision and partial or complete extraction using specific procedure codes for reimbursement. Among the total population of beneficiaries undergoing CIED procedures, International Classification of Diseases codes (ICD 10 GM), operational and procedural codes for partial or complete hardware removal were used to identify CIED infections and lead related endocarditis. To report the corresponding mortality rates, the hospital discharge status was documented. In 2015, from a population of more than 27 million beneficiaries, we identified the cohort of 60,296 patients (57.3% male) who underwent any invasive CIED procedure. Within three months from the index procedure, 1,595 patients developed a major CIED infection. 1,129 (1.87%) were related to the generator pocket and 466 (0.8%) were related to the transvenous proportions of the leads, mortality after those infections was 8.4% and 15.24%, respectively. In summary, our data reveals a higher prevalence of acute CIED infection than previously noted. The elevated number of additional procedures in cases of CIED infection implies a deficiency in infection awareness.

Zwitterionic, amphiphilic polymer coatings are an effective strategy to decrease biofouling. Yet their performance strongly depends on the mechanical properties, the degree of swelling, and the structure of the swollen hydrogels. These properties depend on the zwitterionic groups in the polymers and the properties of the surrounding electrolyte. Therefore, the influence of the ions present and their concentrations on the swelling behavior of amphiphilic zwitterionic copolymers is studied. Coatings of 3‐[N‐2′‐(methacryloyloxy)ethyl‐N,N‐dimethyl]‐ammoniopropane‐1‐sulfonate (SPE) with increasing amounts of butyl‐methacrylate (BMA) are compared to the respective homopolymers PSPE and PBMA. Surface plasmon resonance spectroscopy shows a salt concentration‐dependent anti‐polyelectrolyte behavior. A variation of the salts revealed that the anions dominated the swelling response, while a change of cations has hardly any effect. Small angle X‐ray scattering reveals the morphological changes in the polymer films that accompanied the swelling. With increasing salt concentration, the internal structure changed from compact pores in a gel‐like network to elongated cylindrical pores at higher salinities. The understanding gained from the presented multi‐technique approach allows to understand the behavior of zwitterionic coatings in saline solutions and helps to tailor the swelling response and mechanical properties for future marine and medical low‐fouling applications.

Background Worldwide, the threat of infections linked to cardiovascular implantable electronic devices (CIEDs) is escalating, yet current data regarding infection rates are limited. This study seeks to offer a comprehensive understanding of the frequency of acute CIED-related procedures, hospitalisations stemming from CIED infections, and the resulting mortality rates in Germany. Methods Analysis was performed on data sourced from Germany’s largest healthcare insurance fund to identify CIED procedures conducted in 2018. (Figure 1) This encompassed device placements, revisions, generator substitutions, upgrades, downgrades and extractions. Specific procedure (OPS) and international classification of diseases 10th version German modification codes were employed to pinpoint occurrences of CIED infections and lead-related endocarditis within the beneficiary population. Furthermore, the hospital discharge status was documented. Results In 2018, a collective sum of 53,066 patients (58.1% males) underwent a spectrum of invasive procedures pertaining to CIEDs. Within this cohort, 1.92% necessitated admission either due to localised CIED infections or subsequent development of such infections within a three-month timeframe post-procedure. The manifestation of these localised infections increased the mortality rate, reaching 8.7%. Additionally, 0.84% of patients required hospitalisation attributable to lead-related endocarditis, resulting in a mortality escalation to 17.4%.Patients with CIED pocket infections and lead-related endocarditis tended to be younger (median age 70.7 and 67.3 years vs. 73.7 years) and were more frequently male (68.6% and 71.4%, respectively vs 58.1%). On average, CIED infections led to 2.56 additional procedures per patient, while lead-related endocarditis led to 2.24 additional procedures per patient. Conclusions This study brings attention to a heightened frequency of acute CIED infections compared to previous observations. The occurrence of multiple additional procedures may indicate a potential failure to adhere to CIED infection management guidelines, potentially impacting patient outcomes. • Download figure • Open in new tab • Download powerpoint Abstract 18 Figure 1 CIED procedures conducted in 2018

Background Decreases in symptom load and improvements in quality of life are important goals in the invasive treatment of symptomatic chronic coronary syndrome (CCS). To date, it is not known which patients profit most from the invasive treatment. Methods This sub-analysis of the prospective, multi-centre PLA-pCi-EBO trial includes 145 patients with symptomatic CCS and successful PCI. The prespecified endpoints angina pectoris and quality of life (Seattle Angina Questionnaire–SAQ) were assessed 1 and 6 months after PCI. Predictors of symptom improvement were analyzed by logistic regression analysis. Results Quality of life, physical limitation, and angina frequency markedly improved 6 months after PCI. Worse baseline health status (i.e., low SAQ subscales) was the best predictor of highly clinically relevant improvements (≥ 20 points in SAQ subscales) in symptom load and quality of life. Demographic factors (age, sex, body-mass index) and cardiovascular disease severity (number of involved vessels, ejection fraction) did not predict relevant improvements after PCI. The influence of psychologic traits has not previously been assessed. We found that neither optimism nor pessimism had a relevant effect on symptomatic outcome. However, patients who exercised more after PCI had a much larger improvement in quality of life despite no differences in physical limitation or angina frequency. Conclusion PCI effectively reduces symptom load and improves quality of life in patients with symptomatic CCS. Reduced baseline health status (symptom load, quality of life) are the only relevant predictors for improvements after PCI. Physical activity after PCI is associated with greater benefits for quality of life. Trial registry The German Clinical Trials Register registration number is DRKS0001752.

The present research explores theoretical and computational aspects of the morphological instability ofKirkendall voids induced by a directed flux of vacancies. A quantitative phase-field model is coupled witha multi-component diffusion model and CALPHAD-type thermodynamic and kinetic databases to obtaina meso-scale description of Kirkendall void morphologies under isothermal annealing. The material underinvestigation is a diffusion couple consisting of a multi-phase multi-component single-crystal Ni-basedsuperalloy on one side and pure Ni on the other side. The flux of the fast diffuser Al towards the pureNi causes a strong flux of vacancies in the opposite direction. This directed flux of vacancies leads tomorphologically instable growth of voids, known as Mullins–Sekerka instability. Phase-field simulationsare performed in two (2D) and three dimensions (3D) to understand these instabilities, and the resultsare compared with experimental observations obtained by synchrotron X-ray tomography. Finally, thesimulation results are analyzed with respect to the Mullins–Sekerka linear stability criterion.

Background Both the risk of developing heart disease and the course of the disease are determined in particular by comorbidities. In this context, gout has recently been identified as an important factor in influencing the development of cardiovascular events such as heart failure or coronary artery disease. Methods This retrospective cohort study compared the incidence of angina pectoris (AP) (ICD-10: I20), myocardial infarction (MI) (ICD-10: I21, I22), chronic coronary heart disease (CHD) (ICD-10: I25), atrial fibrillation (AF), and heart failure (HF) as a function of gout in Germany in a large collective of 66,000 gout patients in comparison to 66,000 individuals without gout between using propensity score matching (1:1) from January 2005 to December 2020. Results Within 10 years after the index date, AP was diagnosed in 5.2% of gout and 2.9% of non-gout patients (p < 0.001), MI in 3.1% of gout and 2.2% of non-gout patients (p < 0.001), CHD in 16.5% of gout and 11.8% of non-gout patients, AF in 12.6% of gout and 8.4% of non-gout patients (p < 0.001), and HF in 14.7% of gout and 8.5% of non-gout patients (p < 0.001). For all diagnoses except CHD, the association was stronger in male than in female patients. Conclusion The relationship shown between gout and cardiovascular disease indicates that gout could be one of a series of inflammatory conditions that increase the risk of cardiac disease. The association we have shown between gout and all major cardiac diseases suggests that there is a risk modifier, the treatment of which could help prevent these diseases. Further research is needed to determine whether treating gout can effectively reduce this risk.

Introduction Cardiac implantable electronic device (CIED) complications present significant challenges in clinical practice, especially in elderly patients with multiple comorbidities. Common adverse events include infection, lead malfunction, and device migration. Twiddler’s Syndrome, a rare but serious CIED complication characterised by patient manipulation causing lead displacement and device malfunction, is often underreported. The literature consists mainly of case reports and small series, providing limited guidance on prevention and management. As CIEDs are critical for managing cardiac arrhythmias and heart failure, understanding and addressing Twiddler’s Syndrome is essential. This case report aims to contribute to the literature by detailing a case of Twiddler’s Syndrome, emphasising the importance of a multidisciplinary approach for optimal management. Case Presentation A 59-year-old male presented with discomfort around his implantable cardioverter defibrillator (ICD) site and the sternal area over the past two days. He denied pain, dyspnoea, or dizziness. Clinical examination revealed a normal heart rhythm and no peripheral pulse deficit. Ultrasound revealed a reduced left ventricular ejection fraction. The atrial lead was not visible, and the shock coil was misplaced. ICD interrogation showed inappropriate shocks due to sensing artifacts and exit block in both leads, with no arrhythmias detected. An X-ray confirmed lead dislodgement and significant entanglement in the pocket. The patient was diagnosed with Twiddler’s Syndrome and scheduled for surgical revision. Discussion/Conclusions Dilated cardiomyopathy (DCM), characterised by left ventricular dilatation and dysfunction, accounts for a significant proportion of systolic heart failure cases. Despite advancements in heart failure management, DCM patients remain at high risk for sudden cardiac death (SCD), making ICD implantation crucial. However, CIED placement carries risks of complications, including Twiddler’s Syndrome. This condition can lead to lead dislodgement and device malfunction, resulting in inappropriate shocks and potential patient harm. In this case, a single-session extraction and re-implantation were successfully performed using a multidisciplinary approach, emphasising the importance of comprehensive management strategies to address such complications effectively. Regular follow-up showed no adverse events, highlighting the procedure’s success and the potential benefits of using advanced antimicrobial adjuncts to prevent infections. This case underscores the need for awareness and standardised protocols for managing Twiddler’s Syndrome to improve patient outcomes in the growing population of CIED recipients.

The management of cardiovascular implantable electronic devices (CIEDs) and complex interventions like minimally invasive left ventricular (LV) reduction presents significant challenges and potential adverse events. CIEDs, such as pacemakers and implantable cardioverter-defibrillators (ICDs), are vital for managing arrhythmias and preventing sudden cardiac death but can lead to complications including infections, lead dislodgement, and mechanical failures. Minimally invasive LV reduction procedures, aimed at improving cardiac function in heart failure patients, also carry risks such as residual shunts, arrhythmias, and damage to cardiac structures. The combination of surgical and percutaneous techniques in these procedures adds to the complexity. This case study of a 38-year-old patient undergoing LV reduction and subsequent ICD revision illustrates the delicate balance between therapeutic benefits and potential risks of modern era interventions.

Computational research methods, such as finite element analysis (FEA) and musculoskeletal multi-body simulation (MBS), are important in musculoskeletal biomechanics because they enable a better understanding of the mechanics of the musculoskeletal system, as well as the development and evaluation of orthopaedic implants. These methods are used to analyze clinically relevant issues in various anatomical regions, such as the hip, knee, shoulder joints and spine. Preoperative simulation can improve surgical planning in orthopaedics and predict individual results. In this article, the methods of FE analysis and MBS are explained using two practical examples, and the activities of the “Numerical Simulation” cluster of the “Musculoskeletal Biomechanics Research Network (MSB-NET)” are presented in more detail. An outlook classifies numerical simulation in the age of artificial intelligence and draws attention to the relevance of simulation in the (re)approval of implants.

Event-based semantic segmentation (ESS) is a fundamental yet challenging task for event camera sensing. The difficulties in interpreting and annotating event data limit its scalability. While domain adaptation from images to event data can help to mitigate this issue, there exist data representational differences that require additional effort to resolve. In this work, for the first time, we synergize information from image, text, and event-data domains and introduce OpenESS to enable scalable ESS in an open-world, annotation-efficient manner. We achieve this goal by transferring the semantically rich CLIP knowledge from image-text pairs to event streams. To pursue better cross-modality adaptation, we propose a frame-to-event contrastive distillation and a text-to-event semantic consistency regularization. Experimental results on popular ESS benchmarks showed our approach outperforms existing methods. Notably, we achieve 53.93% and 43.31% mIoU on DDD17 and DSEC-Semantic without using either event or frame labels.