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Item Interprofessionelle perioperative Betreuung von chronischen Dialysepatienten(2025) Köhli, SandraDie komplexe Pharmakotherapie von Dialysepatienten erhöht das Risiko für arzneimittelbezogene Probleme (ABP) sowie die Mortalität und das kardiovaskuläre Risiko im Zusammenhang mit operativen Eingriffen. Ziel des BMG geförderten Projektes war es zu prüfen, ob eine intensivierte, interdisziplinäre Betreuung durch ein Stewardship Team aus Pharmazeuten, Nephrologe und Infektiologe die ABP im Vergleich zum Standard of care verringert.Item Item Physiotherapie in Deutschland(2025) Stöckl, MartinaDie Fragestellung der vorliegenden Arbeit lautet: Wie gestalten sich die Entwicklungsmöglichkeiten der Physiotherapie am Beispiel von Deutschland? Diese resultiert aus einem Forschungsinteresse hinsichtlich zweier Blickrichtungen. Eine empirische, für welche die beiden Checklisten CROSS und COREQ verwendet werden. Die zweite Blickrichtung fokussiert den theoretischen Rahmen der Physiotherapie. Zuerst werden mit dem Fragebogen des sequentiell vertiefenden Mixed-Methods-Designs Informationen über die Durchführbarkeit von physiotherapeutischen Tätigkeiten gesammelt. Dafür werden 120 Physiotherapeut*innen befragt, welche zusätzlich zur Bedeutung der Physiotherapie als Profession Auskunft geben. Sechs Experteninterviews vervollständigen den Datensatz und tragen zur gesamtheitlichen Darstellung der physiotherapeutischen Realität in Deutschland bei. Diese Auswertung erfolgt anhand einer strukturierenden qualitativen Inhaltsanalyse nach Kuckartz mit dem Programm MAXQDA. Zusätzlich wird eine Triangulation aller erhobenen Daten vorgenommen. Die Ergebnisse des Surveys zeigen viele unausgeschöpfte Potenziale im beruflichen Alltag sowie eine enge Sicht auf die Vorstellung der Profession. Die Antworten der befragten Expert*innen bestätigen: Die Physiotherapie ist ein hochkomplexes Gebiet. Mithilfe des in der Arbeit entwickelten dreidimensionalen Pyramidenmodells kann eine Verortung der physiotherapeutischen Realität in ihrer Gesamtheit erfolgen. Zudem kristallisieren sich vielfältige Entwicklungsmöglichkeiten in Richtung Professionalisierung und wissenschaftlicher Disziplinbildung heraus. Eine Übertragung des entwickelten Modells auf andere Berufsgruppen zur Vereinfachung interprofessioneller Zusammenarbeit ist denkbar, ebenso wie eine Anwendung auf internationaler Ebene.Item Item Performance of transcatheter heart valves in severely calcified aortic valve stenoses(2025-06-12) Bisht, OsamaItem Kalorienarme Saccharidzusammensetzung vor der Hauptmahlzeit reduziert die nachfolgende Kalorienaufnahme(2025) Thordsen, Narona LizaItem Behandlung der Harnsäurelithiasis in Deutschland(2025) Genske, Tobias FrankItem Die Komplexität moralischer Erfahrungen mit Palliativer Sedierung(2025) Rau, Franziska JulianaItem Effizienzevaluation von Diagnostikempfehlungen eines molekularen Tumorboards(2025) Tiemann, Paul LennartItem Molecular characterization of breast cancer in patients aged 50 years and older with respect to prognostication, genomic instability, and tumor heterogeneity(2025) Liegmann, Anna-SophieDespite the majority (70%) of female breast cancer cases being diagnosed in women aged 55 years and older and an increasing population of older breast cancer patients due to demographic change, older patients lack adequate representation in cancer research. Thus, this doctoral thesis focused on breast cancer patients aged 50 years and older, aiming to elucidate the role of intratumor heterogeneity, ploidy, and genomic instability and their influences on disease outcome. Therefore, a breast cancer collective of 39 patients with short (median 2.4 years) and long survival (median 19 years) were selected. Multiplex interphase fluorescence in situ hybridization (miFISH) was carried out to analyze copy number alterations (CNAs) of eight breast cancer-associated genes for their potential as biomarkers, as well as assessing genomic instability and tumor heterogeneity. Furthermore, image cytometry was performed to detect ploidy and phylogenetic tree modeling to gain more information about tumor development. Supplementary, targeted next-generation sequencing of 563 breast cancer-associated genes was carried out externally, and the obtained mutation status was statistically analyzed, compared to the miFISH results, and interpreted as part of this thesis. The experimental part of this work revealed several CNAs of breast cancer-specific genes, as well as gene mutations frequently reported in breast carcinomas. The copy number gain of COX2 occurred most frequently (in 72% of the cases), followed by MYC (69%), whereas losses were more common for CDH1 (74%) and TP53 (69%). Comparing aneuploid with diploid tumor samples, significantly higher average signal numbers, CNAs, and instability indices, reflecting the degree of genomic instability, were revealed in the aneuploid tumors. In 16 cases, the signal pattern indicated the formation of an isochromosome 8q and in 14 cases of an isochromosome 17q. Supporting the hypothesis of an isochromosome formation, CNAs of DBC2/MYC and HER2/TP53 significantly co-occurred. Moreover, significant co-occurrence of CNA of HER2/DBC2 was detected, and CNAs for HER2 and PIK3CA mutations and CNAs for CCND1 and PIK3CA mutations were significantly mutually exclusive. Overall, the distribution of gene mutations of the 563-breast cancer-associated genes, as well as the pattern of CNAs in the eight breast cancer-related genes (miFISH) detected in the 39 patients aged 50 years and older, were comparable to results of the age-unbiased TCGA-cohort. Notably, neither the quantity of CNAs, the tumor ploidy, nor the degree of intratumor heterogeneity revealed an association with the survival time, indicating that for patients above the age of 50, these criteria do not seem to have a substantial effect on disease prognosis.Item Evaluation von ophthalmologischen und systemischen Endpunkten nach Strahlentherapie des posterioren uvealen Melanom(2025) Erikson, KristinaDas posteriore uveale Melanom (UM) ist der häufigste intraokuläre primär maligne Tumor, mit 3-5 % Anteil an den malignen Melanomen insgesamt weltweit. Dieses systematische Review konzentriert sich aus klinisch relevanten Gründen auf das Aderhautmelanom und das Ziliarkörpermelanom (zusammengefasst als UM). Bisher gibt es neben altbekannten chirurgischen Methoden, wie der Enukleation, eine Vielzahl an strahlentherapeutischen Möglichkeiten für die Behandlung des UMs. Trotz hinreichender Studienlage ist es bisher allerdings noch nicht gelungen, eindeutig zu identifizieren, welche der Strahlentherapien einen Vorteil in Hinblick auf wichtige klinische Endpunkte, wie die lokale Tumorkontrolle, Metastasierung, Überleben, Visus, Augenerhalt und Strahlennebenwirkungen, hat. Ziel dieser systematischen Übersichtsarbeit und Metaanalyse ist daher der Vergleich der vorhandenen Studienlage, mit Fokus auf die oben genannten klinischen Endpunkte, unter Berücksichtigung der Strahlendosis. Die methodische Vorgehensweise orientiert sich an dem „Cochrane Handbook for Systematic Reviews“ (83). Die Registrierung wurde bei Prospero unter der ID CRD42022311758 durchgeführt. Geeignete Kriterien für den Einschluss relevanter Studien wurden mittels des PICO-Schemas festgelegt. Die PubMed-Datenbank wurde nach Studien durchsucht, die zwischen dem 1. Januar 2000 und dem 31. Dezember 2021 veröffentlicht wurden. Es wurden 20 Studien (18 pro- und retrospektive Kohortenstudien und 2 RCTs) für die weitere Betrachtung identifiziert. Diese flossen in die kritische Bewertung der Studienqualität (Risk of Bias) fand mit den validierten Instrumenten der Cochrane Collaboration ROBINS-I (für nicht-randomisierte Studien) und RoB 2 (für RCTs) ein. Die Metaanalyse für 10 der Studien wurde mit dem Programm R (R-Version 4.1.3, library: meta, procedure: metaprop) (109) durchgeführt. In die Gesamtbewertung fließen die Ergebnisse der Risk of Bias Bewertung, die in der Heterogenitätsanalyse ermittelten Variablen als zusätzliche Einflussgrößen, sowie die in den Forest Plots dargestellten gepoolten Effektschätzer ein. Der kritischste Punkt bei der Erarbeitung unserer Ergebnisse war das Fehlen eines adäquaten Strahlendosisprotokolls mit Angabe der BED und/oder der EQD2. Für die Zukunft sollten Studien prospektiv und randomisiert geplant werden und neben der Angabe der Bestrahlungsdosis pro Augenstruktur auch standardisierte Behandlungsparameter beinhalten, sowie ein einheitliches Nachverfolgungsprotokoll mit eindeutigen, reproduzierbaren Messgrößen.Item Hochgradige Aortenklappenstenose mit normaler Ejektionsfraktion(2025) Kurniadi, AriefItem Das Entlassmanagement in der Onkologie und Palliativmedizin(2025) Kox, Ora-ElenaItem Rotational atherectomy of heavily calcified coronary lesions(2025) Mankerious, NaderCoronary artery calcifications precent in about one fifith of all percutaneous coronary intervention (PCI) procedures [1]. Despite considerable advancements in PCI tools and techniques, coronary calcification remain a significant clinical challenge [2]. Heavily calcified lesions predispose to suboptimal final PCI results [3, 4], underscoring the need for enhanced strategies and tools to adress this challenge. Modified baloons (MB) (cutting and scoring balloons) serve as valuable tools for modifying calcified lesions prior to stent implantation [7]. Nevertheless, these strategies do not achieve optimal plaque modification in over 12% of cases [10, 11]. This highlights the role of rotational atherectomy (RA), which ablates the calcified plaque into small particles (<10 μm), reducing the calcium burden of the lesion and facilitating stent delivery and expansion, potentially improving the long-term performance of drug-eluting stent (DES) [12]. Procedural complications are known to be more frequent among the RA PCIs performed in heavily calcified lesions compared to other PCIs conducted in mild or non-calcified lesions without the use of RA [13]. The SYNTAX score is an anatomically based tool reflecting the cumulative complexity of the coronary tree, taking into account their specific locations and characteristics [15]. We hypothesized that determining the SYNTAX score for the target vessel in the context of RA may serve as a predictive tool for the likelihood of in-hospital adverse outcomes by predicting the technical difficulties faced during the PCI. We have developed the new concept of target vessel SYNTAX score (tvSS) to adress this point. Our analysis aimed to explore the predictors of in-hospital adverse outcomes after RA and to test the target vessel SYNTAX score (tvSS) as a potential causal variable [46]. Patients receiving RA were divided into two groups according to the occurrence of in-hospital adverse outcomes. Median TvSS was significantly higher in patients with vs. without in-hospital adverse outcomes. A tvSS cut-off value of 15 showed 73% sensitivity and 62% specificity for predicting in-hospital adverse outcomes. Moreover, a tvSS ≥15, bailout RA, reduced LVEF, as well as diabetes mellitus, emerged as independent predictors of in-hospital adverse outcomes. After one year follow-up, there was no significant difference between patients with vs. without in-hospital adverse outcomes regarding the rates of composite MACE, all-cause death, MI and TVR. Coronary bifurcation lesions present complex anatomical challenges in the field of interventional cardiology, observed in up to 20% of all PCI cases [18, 19]. They are complex anatomical structures where the main vessel and the side branch (SB) are interpolated within a bifurcation segment [20]. SB compromise is an early described complication during PCI of bifurcation lesions [22]. Main vessel plaques can cause plaque shift leading to side branch compromise [25]. However, the plaque nature including the presence of calcification is also an important predictor of the side branch compromise [26, 27]. The PREPARE-CALC multicenter randomized controlled trial investigated lesion preparation strategies for severely calcified coronary lesions, comparing the use of a MB versus RA, followed by implantation of biodegradable polymer sirolimus eluting stent [11]. We conducted an as-treated subgroup analysis of bifurcation lesions from the PREPARE–CALC trial [47]. We compared outcomes of different modification techniques of severly calcified bifurcation lesion. At the end of the procedure, the SB remained significantly compromised in 15 lesions in MB (32%) and in 5 lesions (7%) in RA group. Fluoroscopy time and procedural duration were significantly higher in RA group. Large coronary dissections were more frequently observed in MB group. In-hospital outcome was similar between both groups. Additionally, we analyzed the evolution of cardiac biomarkers in patients with (n=20) and without (n=84) compromised SB at the end of the procedure until 24 hours. The median value of CK-MB was significantly higher at 16H post-PCI in compromised SB patients with a trend towards higher Troponin T. CTO is observed in approximately one-fifth of all PCI [28]. Heavily calcified CTO lesions present a challenge in CTO PCI and are not uncommon. In fact, moderate to severe calcification characterizes over half of the CTO lesions [29]. The use of RA for the preparation of calcified CTO lesions is increasing [30]. The feasibility and in-hospital outcome of RA in CTOs were reported in some studies [32, 33]. We investigated the in-hospital and long-term outcomes after RA for CTO compared to non-CTO calcified lesions [48]. The angiographic success was less in CTO RA procedures, and the procedural success rate was 80% versus 90.5% in CTO RA versus non-CTO RA procedures. In-hospital MACE was comparable in both groups. However, the incidence of slow flow, coronary perforation and cardiac tamponade were higher in the CTO RA group. We observed a higher 2-year TLF in the CTO group, that was driven by higher cardiac deaths. However, target vessel MI and clinically driven TLR rate were comparable between the study groups. On multivariate regression analysis, the presence of CTO lesion, chronic kidney disease (CKD), periprocedural MI and reduced LV-EF (EF < 50%) were independently associated with the two-year TLF. In the CTO group, 38.7% of patients were treated with elective RA. Compared to elective RA, bail-out procedures took longer time, had higher number of dissections and more frequently required two or more burrs. However, the estimated rate of 2-year TLF was not significantly different between those received elective RA and bailout RA. In conclusion, the use of RA is expanding and reaching high-risk populations. In-hospital adverse outcomes during RA are common in patients with more complex target vessel anatomy as indicated by a higher target vessel SYNTAX score (tvSS ≥ 15). Additionally, bailout RA and left ventricular systolic function emerged as predictors of in-hospital adverse outcomes. In-hospital adverse outcomes were not associated with long-term MACE. In the context of high-risk lesions, comparing a strategy of MB versus RA in severely calcified coronary bifurcation lesions, we observed a significantly higher rate of side branch compromise with an MB-based strategy, which did not translate into worse short-term clinical outcome. Side branch compromise was associated with more extensive periprocedural myocardial injury. Therefore, in calcified bifurcation lesions, an upfront debulking with an RA-based strategy might optimize the result of PCI in the side branch. Furthermore, RA in CTO is feasible with a high success rate. However, the long-term outcome is worse than non-CTO RA. Elective RA in CTO can shorten the procedure time and decrease the incidence of dissection in comparison with bail-out RA. Finally, RA is an indispensable modality in every catheterization laboratory and may be the only solution for lesion preparation in heavily calcified cases, especially in situations where PTCA balloons are unable to cross or dilate the lesion.