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Impact of Becoming a Certified Oncologic Center of Pancreatic Surgery: Evaluation of Single-Center Perioperative Results and Quality of Life Before and After Implementation of a Certified Center
Get PDFCentralization and certification mark constant processes in everyday clinical routine. Despite the continuously rising number of certified pancreatic cancer (PAC) centers in recent years, fewer than 40% of PAC resections are still performed in certified institutions nationwide. The main objective of the certification is the enhancement of patient survival. Furthermore, certification is intended to improve structural quality, multidisciplinary cooperation, and the transparency of treatment pathways. [...] However, it requires the substantial effort of all partners involved. We aim to illustrate both advantages and limitations of the certification process. The study cohort included 47 patients treated in the three years prior to certification and 130 patients during the subsequent seven years as a certified center. The mean annual number of PAC resections increased from 15 (ranged 14-18) to 19 (ranged 10-26). In-hospital mortality, length of stay, and rate of exploration-only procedures remained unchanged. Indicators of procedural quality, such as the number of harvested lymph nodes (p = 0.1485) and the precision of histopathological assessment, improved slightly but not significantly. QoL scores generally improved after discharge in both groups; however, functional scales and symptom measures demonstrated unexpectedly inferior values following certification, possibly reflecting higher case complexity. Achieving and maintaining certification requires substantial and continuous effort from all disciplines involved. While major improvements in morbidity, mortality, and long-term QoL were not observed, certification ensured clearer delegation of responsibilities, standardized documentation, and structured quality control. We therefore consider the certification process valuable for promoting multidisciplinary collaboration, maintaining high treatment volumes, and ensuring transparent oncological care pathways
Mpox: Exploring Epidemiology, Disease Outcomes, and Preventative Vaccination Among People with HIV During the Ongoing Outbreaks
Get PDFHuman mpox, caused by the mpox virus, is a reemerging viral zoonosis that has gained global attention due to recent Clade IIb outbreaks outside of Africa, as well as ongoing Clade Ia and Ib outbreaks in the Democratic Republic of Congo (DRC) and surrounding regions. Since the start of these outbreaks in 2022, approximately 160,000 people have been affected across more than 100 countries. People with human immunodeficiency virus (HIV; hereafter referred to as PWH) have been disproportionately affected, accounting for approximately 50% of all cases. Mpox is typically a self-limiting illness causing smallpox-like symptoms lasting 2–4 weeks, which can cause significant pain and morbidity. People with uncontrolled or advanced HIV face an elevated risk of severe mpox, secondary complications, and worse outcomes. Vaccination with second- and third-generation vaccinia-based smallpox vaccines has emerged as an important tool in mpox prevention, alongside behavioural modification to mitigate risk. However, only the third-generation, live-attenuated, non-replicating vaccine, modified vaccinia Ankara (MVA-BN [Bavarian Nordic]), is approved for use in PWH. Real-world estimates suggest that two doses of MVA-BN administered as pre-exposure prophylaxis confers vaccine effectiveness in the range of 66–90%. Additionally, MVA-BN has been widely demonstrated to have an acceptable safety profile. This narrative review explores the changing epidemiology, clinical manifestations, and outcomes of mpox in PWH. We also summarise evidence from the Clade IIb outbreaks on the effectiveness and safety of MVA-BN among PWH. Despite progress in our understanding, knowledge gaps persist regarding vaccine performance in individuals with advanced immunosuppression. [...] These insights may be helpful in the planning of future research and to inform strategies for the prevention and management of mpox among PWH, particularly those with advanced or uncontrolled HIV
The Emerging Role of Multimodal Artificial Intelligence in Urological Surgery
Get PDFArtificial intelligence (AI) is transforming urological oncology surgery. While earlier systems were mainly limited to analyzing image data, modern multimodal models can combine various sources of information, such as imaging, laboratory values, robotic data and clinical documentation. This allows for more precise diagnostics, surgical planning and follow-up care. Generative AI can also enhance communication between physicians and patients, as well as support surgical training by providing realistic simulations and personalized feedback. However, there are risks associated with incomplete or distorted training data, data protection issues and unclear responsibilities in AI-supported decision-making. A better understanding of the opportunities and limitations of multimodal and generative AI is crucial to ensure its safe, ethical and clinically meaningful use in urological practice
Bias-Corrected Root Mean Square Deviation Estimators
Get PDFThe root mean square deviation (RMSD) is a widely used item fit statistic in item response models. However, the sample RMSD is known to exhibit positive bias in small samples. To address this, seven alternative bias-corrected RMSD estimators are proposed and evaluated in a simulation study involving items with uniform differential item functioning (DIF). The results demonstrate that the proposed estimators effectively reduce the bias of the original RMSD statistic. Their performance is compared, and the most favorable estimators are highlighted for empirical research. Finally, the application of the various RMSD statistics is illustrated using PISA 2006 reading data
Proteolytische Regulation von PGAM5 in nicht-apoptotischem Zelltod
Get PDFThe understanding of cell death has shifted from a distinction between apoptosis and necrosis to a diverse landscape of regulated pathways. This thesis focuses on two such pathways, necroptosis and parthanatos, both relevant in conditions like hypoxia-induced damage and neurodegenerative disease. Necroptosis, described in 2005, depends on RIPK3 and MLKL, but other factors also modulate this process. Among them, PGAM5 was initially proposed as essential, though later studies challenged this. Here, PGAM5 was shown to accumulate strongly in murine L929Ts C47 fibrosarcoma cells undergoing necroptosis. This applied to both endogenous and transfected PGAM5, suggesting proteolytic regulation rather than transcriptional regulation. Consistent with this, inhibition of the proteasome - via MG-132, the E1 ubiquitin-activating enzyme inhibitor Pyr-41, or siRNA targeting PSMC4 - led to marked increases in PGAM5 levels. These findings support a proteasome-dependent regulation of PGAM5. Although the precise role of elevated PGAM5 during necroptosis remains unclear. A second aim was to examine whether the mitochondrial rhomboid protease PARL contributes to necroptosis. PARL typically cleaves PINK1 but can shift to PGAM5 when mitochondrial membrane potential is lost. Mouse embryonic fibroblasts lacking PARL or reconstituted with PARL-FLAG showed no difference in necroptotic sensitivity, suggesting PARL is dispensable for this pathway. Parthanatos, driven by PARP1 activity, was also examined to determine whether PGAM5 or the mitochondrial protease HtrA2 participate in this death mechanism. L929Ts cells deficient in PGAM5 or HtrA2 were exposed to the alkylating agent MNNG. While PGAM5 loss had no effect, HtrA2 deficiency strongly reduced parthanatos, indicating that HtrA2 is involved in this cell death pathway and represents a promising target for further study
Multibeam-Datenanalyse: Automatisierte Erkennung von Meeresboden-Anomalien und Seamounts zur Verbesserung des Verständnisses von Meeresbodenprozessen
Get PDFThis dissertation demonstrates that combining ensemble-based quality control with machine-learning–driven feature detection enables robust, scalable, and auditable analysis of large multibeam echosounder bathymetry datasets. By substantially reducing operator-dependent intervention while preserving expert traceability, the proposed methods improve consistency across surveys, regions, and sensors and facilitate the discovery of previously unresolved geomorphic features. Beyond seafloor mapping, the presented design principles are broadly transferable to other large-scale geospatial raster analyses. Future developments integrating backscatter information and weakly supervised learning promise further gains in interpretability, coverage, and efficiency, supporting next-generation, data-driven seafloor exploration
Nachhaltige Implementierung von Shared Decision Making in kompletten Versorgungszentren mit dem SHARE TO CARE-Programm
Get PDFShared Decision Making (SDM) gewinnt in der medizinischen Versorgung zunehmend an Bedeutung, da es die aktive Einbindung von Patient*innen in Entscheidungsprozesse fördert. SDM unterscheidet sich von informierter Einwilligung, indem es einen Austausch zwischen Arzt und Patient auf Augenhöhe ermöglicht. Patient*innen bringen ihre Erwartungen, Präferenzen und Lebensumstände in den Entscheidungsprozess ein. Studien zeigen, dass SDM zu höherer Patientenzufriedenheit, besserer Adhärenz und gesteigerter Gesundheitskompetenz führt. Die Neuromedizin ist besonders geeignet für die Anwendung von SDM, da Patient*innen oft mit chronischen und progressiven Erkrankungen konfrontiert sind und eine langfristige Zusammenarbeit mit dem medizinischen Team notwendig ist. Zur nachhaltigen Implementierung von SDM wurde das SHARE TO CARE-Programm entwickelt. Das Programm umfasst vier Interventionsbausteine: SDM-Training für Ärztinnen, Online-Entscheidungshilfen, Einbindung von Pflegepersonal und Patientinnenaktivierung. Es wurde über vier Jahre an 17 Kliniken des Universitätsklinikums Schleswig-Holstein (UKSH) implementiert. Die Forschungsergebnisse der Implementierung im Neurozentrum am UKSH, bestehend aus der Klinik für Neurologie und der Klinik für Neurochirurgie, zeigen signifikante Verbesserungen in der Patient*innenbeteiligung nach der Implementierung des S2C-Programms. Artikel 1 dokumentiert eine initiale signifikante Steigerung der Patient*innenbeteiligung (p < .001, Hedges g = .49) und eine verbesserte Vorbereitung auf Entscheidungen (p = .02, Hedges g = .32). Artikel 2 zeigt, dass die positiven Effekte bis zu 18 Monate nach der Implementierung weiterhin signifikant sind (z.B. PICSPDM: p = .02, Hedges g = .33). Die Ergebnisse sind vielversprechend, zeitgleich ist weitere Forschung zur Nachhaltigkeit der SDM-Intervention wünschenswert
Eine retrospektive, monozentrische, epidemiologische Beobachtungsstudie zum Vergleich von Spektrum, Evolution und klinischer Korrelation zerebraler Magnetresonanztomographie (MRT) bei Kindern mit Febrile Infection-Related Epilepsy Syndrom (FIRES)
Get PDFDas „Febrile infection-related epilepsy syndrome“ (FIRES) ist gekennzeichnet durch einen refraktären Status epilepticus wenige Tage nach Beginn einer fieberhaften Erkrankung. Dieser akuten Phase folgt die chronische Phase mit refraktärer Epilepsie und meistens schweren neurologischen Folgeerscheinungen. Während der akuten und chronischen Phase von FIRES wurde die zerebrale Magnetresonanztomographie (MRT) als wichtiges diagnostisches Instrument beschrieben. Hier wurde das Spektrum und der langfristige Zeitverlauf der MRT-Befunde sowie ihre Beziehung zwischen klinischem Verlauf, Komatherapie und Outcome, basierend auf den Daten einer großen Fallserie von Kindern mit FIRES analysiert. Diese Analyse soll helfen herauszufinden, ob es diagnostische, progressive und prognostische MRT-Befunde von FIRES gibt, sowie die Frage beantworten, ob die häufig beobachtete Hirnatrophie mit der Komatherapie zusammenhängt
A Multi-Port Partial Power Converter for PV based Smart Home Applications
Get PDFThe world is undergoing a profound transformation with an increasing penetration of renewable energy sources (RES), expanding from utility-scale projects to residential applications. Power electronic converters (PECs) play a crucial role in enabling advanced energy management in smart homes, allowing residences to operate as intelligent ecosystems. Recently, the integration of RES and residential energy storage systems (ESS) has enabled direct power supply to smart homes through DC-DC conversion, reducing electricity costs and ensuring energy availability during grid outages. Therefore, DC-DC converters have become essential components in smart home architectures. Traditionally, full power processing (FPP) DC-DC converters have been utilized, processing the entire input power. However, partial power processing (PPP) architectures, which process only a fraction of the total power, offer significant advantages in reducing losses, cost, and converter volume. Thus, applying PPP in smart home applications enhances system efficiency and integration. This study develops and analyzes a multi-port PPP converter architecture for smart home applications. The proposed architecture aims to improve efficiency compared to conventional multi-port PPP converters, while reducing cost and volume by using partially rated power electronic devices instead of fully rated FPP devices. To achieve these goals, optimal topologies are explored, and a detailed design guideline for the proposed converter is provided, enabling practical implementation. Furthermore, the relationship between PPP capability and converter losses is analyzed to validate the efficiency improvement. Finally, a prototype of the proposed architecture is implemented, and its steady-state operation, power management capability, and efficiency under different load conditions are experimentally verified, including the peak efficiency
Enhancing Immune Surveillance: Antibody-based Strategies for the Activation and Expansion of Natural Killer (NK) Cells and γδ T cells
No full textNatural Killer cells (NK cells) continuously screen surrounding cells and differentiate between “self” and “missing-self” as well as healthy or stressed/malignant. The activity of NK cells and the corresponding immune response is regulated by a complex interplay of activating and inhibiting receptors and the respective ligands. However, recognition of malignant cells can become difficult when the cells shed the respective signals from the cell surface and thus make themselves invisible to NK cells. In order to restore the recognition of malignant cells and consequently redirect NK cells against malignant cells, antibodies can be used that bind the antigen on tumor cells and activate NK cells by binding to the FcγRIIIa or an activating receptor on NK cells. In the context of this work, novel NK cell engagers (NKCEs) were produced and tested that bridge the epidermal growth factor receptor (EGFR) on tumor cells to NKp30 on NK cells. Once it was established that the bound epitope played a decisive role in the effectiveness of the NKCEs, further attributes of the antibodies were modified to investigate the respective effect of the modification. In addition to the lack of recognition by NK cells, selected patients show a reduced number of effector cells, as well as a certain dysfunction of these. Therefore, an adoptive cell transfer (ACT) of cytotoxic NK cells represents a promising approach to treat these patients. However, the expansion of cytotoxic NK cells is not trivial and often requires the use of genetically modified feeder cells. In this work, a novel technology for the ex vivo expansion of NK cells was established that obviates the need of genetically modified feeder cells and achieved high numbers of cytotoxic NK cells which are well suited for the development of therapies based on ACT