TY - JOUR A1 - Basile, Vittoria A1 - Puglisi, Soraya A1 - Altieri, Barbara A1 - Canu, Letizia A1 - Libè, Rossella A1 - Ceccato, Filippo A1 - Beuschlein, Felix A1 - Quinkler, Marcus A1 - Calabrese, Anna A1 - Perotti, Paola A1 - Berchialla, Paola A1 - Dischinger, Ulrich A1 - Megerle, Felix A1 - Baudin, Eric A1 - Bourdeau, Isabelle A1 - Lacroix, André A1 - Loli, Paola A1 - Berruti, Alfredo A1 - Kastelan, Darko A1 - Haak, Harm R. A1 - Fassnacht, Martin A1 - Terzolo, Massimo T1 - What is the optimal duration of adjuvant mitotane therapy in adrenocortical carcinoma? An unanswered question JF - Journal of Personalized Medicine N2 - A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence. KW - mitotane KW - adjuvant treatment KW - adrenocortical cancer KW - recurrence KW - recurrence free survival KW - timing Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236507 SN - 2075-4426 VL - 11 IS - 4 ER - TY - JOUR A1 - Sequeira, Vasco T1 - When fat meets the engine: implications of dietary rumenic acid on myosin-targeting therapies in heart failure JF - Journal of Physiology N2 - No abstract available. KW - rumenic acid KW - cardiomyopathy KW - mavacamten KW - myosin KW - omecamtiv mecarbil Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259693 VL - 599 IS - 15 ER - TY - JOUR A1 - Fröhlich, Matthias A1 - Serfling, Sebastian A1 - Higuchi, Takahiro A1 - Pomper, Martin G. A1 - Rowe, Steven P. A1 - Schmalzing, Marc A1 - Tony, Hans-Peter A1 - Gernert, Michael A1 - Strunz, Patrick-Pascal A1 - Portegys, Jan A1 - Schwaneck, Eva-Christina A1 - Gadeholt, Ottar A1 - Weich, Alexander A1 - Buck, Andreas K. A1 - Bley, Thorsten A. A1 - Guggenberger, Konstanze V. A1 - Werner, Rudolf A. T1 - Whole-Body [\(^{18}\)F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease JF - Diagnostics N2 - The 2-deoxy-d-[\(^{18}\)F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is widely utilized to assess the vascular and articular inflammatory burden of patients with a suspected diagnosis of rheumatic disease. We aimed to elucidate the impact of [\(^{18}\)F]FDG PET/CT on change in initially suspected diagnosis in patients at the time of the scan. Thirty-four patients, who had undergone [\(^{18}\)F]FDG PET/CT, were enrolled and the initially suspected diagnosis prior to [18F]FDG PET/CT was compared to the final diagnosis. In addition, a semi-quantitative analysis including vessel wall-to-liver (VLR) and joint-to-liver (JLR) ratios was also conducted. Prior to [\(^{18}\)F]FDG PET/CT, 22/34 (64.7%) of patients did not have an established diagnosis, whereas in 7/34 (20.6%), polymyalgia rheumatica (PMR) was suspected, and in 5/34 (14.7%), giant cell arteritis (GCA) was suspected by the referring rheumatologists. After [\(^{18}\)F]FDG PET/CT, the diagnosis was GCA in 19/34 (55.9%), combined GCA and PMR (GCA + PMR) in 9/34 (26.5%) and PMR in the remaining 6/34 (17.6%). As such, [\(^{18}\)F]FDG PET/CT altered suspected diagnosis in 28/34 (82.4%), including in all unclear cases. VLR of patients whose final diagnosis was GCA tended to be significantly higher when compared to VLR in PMR (GCA, 1.01 ± 0.08 (95%CI, 0.95–1.1) vs. PMR, 0.92 ± 0.1 (95%CI, 0.85–0.99), p = 0.07), but not when compared to PMR + GCA (1.04 ± 0.14 (95%CI, 0.95–1.13), p = 1). JLR of individuals finally diagnosed with PMR (0.94 ± 0.16, (95%CI, 0.83–1.06)), however, was significantly increased relative to JLR in GCA (0.58 ± 0.04 (95%CI, 0.55–0.61)) and GCA + PMR (0.64 ± 0.09 (95%CI, 0.57–0.71); p < 0.0001, respectively). In individuals with a suspected diagnosis of rheumatic disease, an inflammatory-directed [\(^{18}\)F]FDG PET/CT can alter diagnosis in the majority of the cases, particularly in subjects who were referred because of diagnostic uncertainty. Semi-quantitative assessment may be helpful in establishing a final diagnosis of PMR, supporting the notion that a quantitative whole-body read-out may be useful in unclear cases. KW - giant cell arteritis KW - GCA KW - [18F]FDG PET/CT KW - vasculature KW - inflammation KW - polymyalgia rheumatica KW - PMR KW - vasculitis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250227 SN - 2075-4418 VL - 11 IS - 11 ER - TY - JOUR A1 - Boelch, Sebastian P. A1 - Gurok, Anna A1 - Gilbert, Fabian A1 - Weißenberger, Manuel A1 - Rudert, Maximilian A1 - Barthel, Thomas A1 - Reppenhagen, Stephan T1 - Why compromise the patella? Five-year follow-up results of medial patellofemoral ligament reconstruction with soft tissue patellar fixation JF - International Orthopaedics N2 - Purpose This study investigates the redislocation rate and functional outcome at a minimum follow-up of five years after medial patellofemoral ligament (MPFL) reconstruction with soft tissue patellar fixation for patella instability. Methods Patients were retrospectively identified and knees were evaluated for trochlea dysplasia according to Dejour, for presence of patella alta and for presence of cartilage lesion at surgery. At a minimum follow-up of five years, information about an incident of redislocation was obtained. Kujala, Lysholm, and Tegner questionnaires as well as range of motion were used to measure functional outcome. Results Eighty-nine knees were included. Follow-up rate for redislocation was 79.8% and for functional outcome 58.4%. After a mean follow-up of 5.8 years, the redislocation rate was 5.6%. There was significant improvement of the Kujala score (68.8 to 88.2, p = 0.000) and of the Lysholm score (71.3 to 88.4, p = 0.000). Range of motion at follow-up was 149.0° (115–165). 77.5% of the knees had patella alta and 52.9% trochlear dysplasia types B, C, or D. Patellar cartilage legions were present in 54.2%. Redislocations occurred in knees with trochlear dysplasia type C in combination with patella alta. Conclusion MPFL reconstruction with soft tissue patellar fixation leads to significant improvement of knee function and low midterm redislocation rate. Patients with high-grade trochlear dysplasia should be considered for additional osseous correction. KW - MPFL KW - medial patellofemoral ligament KW - patella instability KW - patella dislocation KW - trochlear dysplasia KW - patella alta Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235751 SN - 0341-2695 VL - 45 ER - TY - JOUR A1 - Fiore, Piera Filomena A1 - Vacca, Paola A1 - Tumino, Nicola A1 - Besi, Francesca A1 - Pelosi, Andrea A1 - Munari, Enrico A1 - Marconi, Marcella A1 - Caruana, Ignazio A1 - Pistoia, Vito A1 - Moretta, Lorenzo A1 - Azzarone, Bruno T1 - Wilms' tumor primary cells display potent immunoregulatory properties on NK cells and macrophages JF - Cancers N2 - The immune response plays a crucial defensive role in cancer growth and metastasis and is a promising target in different tumors. The role of the immune system in Wilm’s Tumor (WT), a common pediatric renal malignancy, is still to be explored. The characterization of the immune environment in WT could allow the identification of new therapeutic strategies for targeting possible inhibitory mechanisms and/or lowering toxicity of the current treatments. In this study, we stabilized four WT primary cultures expressing either a blastematous (CD56\(^+\)/CD133\(^−\)) or an epithelial (CD56\(^−\)/CD133\(^+\)) phenotype and investigated their interactions with innate immune cells, namely NK cells and monocytes. We show that cytokine-activated NK cells efficiently kill WT cells. However, after co-culture with WT primary cells, NK cells displayed an impaired cytotoxic activity, decreased production of IFNγ and expression of CD107a, DNAM-1 and NKp30. Analysis of the effects of the interaction between WT cells and monocytes revealed their polarization towards alternatively activated macrophages (M2) that, in turn, further impaired NK cell functions. In conclusion, we show that both WT blastematous and epithelial components may contribute directly and indirectly to a tumor immunosuppressive microenvironment that is likely to play a role in tumor progression. KW - Wilm's tumor KW - NK cells KW - macrophages KW - tumor microenvironment KW - Wilms' tumor Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222981 SN - 2072-6694 VL - 13 IS - 2 ER - TY - THES A1 - Chatzidimitriou, Nikolaos T1 - Wird die Behandlung des kindlichen Hydrocephalus durch neue Ventilsysteme verbessert? Ein Vergleich zweier Shuntsysteme T1 - Do new shunt systems improve the treatment of pediatrich hydrocephalus. A comparison between two shunt systems N2 - Der Unishunt der Firma Codman gilt als Niederdruck-System und führt in aufrechter Körperposition zur erheblichen Überdrainage. Das Delta-System der Firma Medtronic hingegen soll durch seinen Ventilmechanismus eine Überdrainage verhindern und den Liquordruck in einem physiologischen Rahmen halten. Die vorliegende Studie untersucht die Frage, ob das Delta-System gegenüber dem Unishunt einen Vorteil hinsichtlich der Überdrainage aufweist, der sich an der revisionsfreien Funktionsdauer zeigt. Unter Berücksichtigung der Ventrikelweite prüften wir insbesondere, ob die Überdrainage und die damit verbundenen Komplikationen verringert werden können. In einer retrospektiven Fall-Sammel-Studie wurden die Patientendaten von 199 Kindern im Alter zwischen einem Tag und 10.4 Jahren ausgewertet, die im Zeitraum vom 01.01.1985 bis 01.03.2002 in der Abteilung für pädiatrische Neurochirurgie der Universitätsklinik Würzburg eine Erstimplantation eines ventrikuloperitonealen oder -atrialen Shunts mit Verwendung eines Unishunts (n= 138) oder eines Delta-Systems (n=61) erhielten. Gewertet wurden alle mechanischen oder infektiösen Komplikationen, die zu einer operativen Shuntrevision führten. Bei den mechanischen Komplikationen unterschieden wir zwischen proximaler Obstruktion, distaler Obstruktion, Migration, Diskonnektion oder Katheterriss, Ventilunterfunktion und Überdrainage. Als Überdrainage wurden operationspflichtige Subduralergüsse, eindeutige Unterdruck-beschwerden und das Slit-Ventricle-Syndrom gewertet. Asymptomatische Subdural-ergüsse und andere nicht operationspflichtige Funktionsanomalien werteten wir nicht als Komplikation. Als Shuntinfektion bezeichneten wir klinische und laborchemische Zeichen einer bakteriellen Infektion, die nach Shuntexplantation abklangen. Die durchschnittliche Funktionsdauer der Shunts wurde in vorliegender Studie durch das Delta-System nicht verlängert. Die kumulative Revisionswahrscheinlichkeit nach einem Jahr betrug beim Unishunt 30.6 %, beim Delta-System 24.9 %, lag aber nach fünf Jahren mit 58.0 % beim Delta-System höher als beim Unishunt (40.9 %). Bei den mechanischen Komplikationen ergab sich als wesentlicher Unterschied zwischen beiden getesteten Systemen eine häufigere distale Blockade des Peritonealkatheters beim Unishunt, die aber durch häufigere Ventilfehlfunktion des Delta-Systems weitgehend ausgeglichen wurde. Die niedrigste Druckstufe führte beim Delta-System signifikant häufiger zu einer proximalen Obstruktion als die höchste. Die eigenen Untersuchungsergebnisse sprechen dafür, dass Delta-Ventile tatsächlich der Neigung zur Überdrainage entgegenwirken, ohne dass sich dieser Vorteil in der Revisionsrate bemerkbar macht. Das Delta-System führt zu einer niedrigeren Überdrainagerate und weniger Überdrainage-assoziierten Erscheinungen wie Subduralergüssen. Dieser Unterschied war am ehesten morphologisch zu erfassen, jedoch im Vergleich zum Unishunt nicht signifikant. Der Unishunt war mit einer höheren Infektionsrate von 11.6 % im Vergleich zum Delta-System (3.3 %) belastet. Der Unterschied lässt sich weder mit konstruktiven Ventilmerkmalen noch mit besonderen Maßnahmen der Infektionsprophylaxe erklären. Der im Vergleich zum Unishunt höhere Preis des Delta-Systems findet keinen Niederschlag in einer niedrigeren Komplikationsrate des Systems. N2 - The Unishunt (Codman) is a low-pressure-system and tends to excessive overdrainage in the erect position. The delta-valve is supposed to prevent overdrainage and to keep CSF in his physiologic limits.This study compares the unishunt-system with the delta-system and examines if there is any advantage regarding overdrainage and if this advantage displays in the revision-free survival of an shunt. We also considered the effect of the different shunt technologies on the ventricle width. In a retrospective analysis we reviewed the medical and surgical charts of 138 children with unishunt system and 61 childeren with delta-system who were treated with a first-time shunt implantation at the department of pediatric neurosurgery,University of Würzburg between 1.1.1985 and 1.3.2002 We considered all mechanical and infectious complications that led to a operative shunt revision. We distinguished between proximal obstruction, distal obstruction, valve obstuction, migration, disconnection or fracture of the catheter and overdrainage. Overdrainage was said to be occured in the presence of symptomatic subdural effusions that needed operative revision and the Slit-ventricle-syndrom. Asymptomatic subdural effusions and other functional anomalies that could be treated consevativly were not considered as overdrainage. Shunt infection was defined as clinical and laboratory signs of a infection that ease off with shunt explantation and antibiotic treatment. Positive Gram stains or cultures were not necessary for the diagnosis of a shunt infection. Results: the overall shunt survival was not influenced by the delta-system. The overall- complication rate in the first year after implantation was 30.6 % for the unishunt and 24.9 % for the delta-valve and 40.9 % and 58 % respectively after 5 years. Overdrainage rate was 1.4 % for the unishunt-system, no shunt revision was necessary for the delta-system, the between the two systems was not signifikant. The advantage of the delta-system concerning overdrainage was seen more morphologically, the normalization or collaps of the ventricles was seen slowlier in the delta-system, the difference to the unishunt-system was not significant. The infection rate was 11.6 % for the unishunt-system and 3.3 % for the delta-system. This difference also was not significant and cannot be explained with the parameters studied. KW - Hydrocephalus KW - Unishunt KW - Delta-Valve KW - Overdrainage Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234729 N1 - Dieses Dokument wurde aus Datenschutzgründen - ohne inhaltliche Änderungen - erneut veröffentlicht. Die ursprüngliche Veröffentlichung war am: 09.07.2005 ER - TY - THES A1 - Tillmann, Carolin T1 - Wirksamkeit und Sicherheit der oralen Propranolol-Therapie bei Säuglingen mit proliferierenden infantilen Hämangiomen: eine retrospektive Untersuchung bei Patienten der interdisziplinären Hämangiomsprechstunde am Universitätsklinikum Würzburg T1 - Efficacy und Safety of oral Propranolol in Infants with proliferating infantile Hemangioma: a retrospective Research of Ratients of the interdisciplinary Hemangioma clinic at University Hospital Würzburg N2 - Die vorliegende retrospektive Untersuchung fasst Ergebnisse bei 69 Säuglingen zusammen, die in den Jahren 2010 bis 2014 aufgrund infantiler Hämangiome mit eingetretenen oder drohenden Komplikationen am Universitätsklinikum Würzburg mit dem Betablocker Propranolol oral behandelt wurden. Ergänzend wurden von 45 der 69 Elternpaare nach Therapieende Fragebögen zur subjektiven Einschätzung der Behandlung ihrer Kinder ausgefüllt. Die Ergebnisse dieser Studie zeigen in Zusammenschau mit zahlreichen Publikationen zu diesem Thema, dass Propranolol bei proliferierenden Säuglingshämangiomen eine sichere und hocheffektive Therapie bei gleichzeitig überschaubaren und nur in Einzelfällen gravierenden Nebenwirkungen hat. N2 - This retrospective research sums up the outcome of 69 infants with complicated hemangiomas being treated with beta blocker Propranolol between 2010 and 2014 at Universitätsklinikum Würzburg. In addition a survey about the subjective experiences with the Propranolol therapy was completed by 45 of 69 parents. Like the findings in literature the results of this research show that Propranolol in the treatment of complicated hemangioma in infants is save and highly effective. KW - Hämangiom KW - Propranolol KW - Propranolol-Therapie KW - infantile Hämangiome KW - interdisziplinäre Hämangiomsprechstunde Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220462 ER - TY - JOUR A1 - Weich, Alexander A1 - Rogoll, Dorothee A1 - Gawlas, Sophia A1 - Mayer, Lars A1 - Weich, Wolfgang A1 - Pongracz, Judit A1 - Kudlich, Theodor A1 - Meining, Alexander A1 - Scheurlen, Michael T1 - Wnt/β-catenin signaling regulates CXCR4 expression and [\(^{68}\)Ga] Pentixafor internalization in neuroendocrine tumor cells JF - Diagnostics N2 - Loss of Somatostatin Receptor 2 (SSTR2) expression and rising CXC Chemokine Receptor Type 4 (CXCR4) expression are associated with dedifferentiation in neuroendocrine tumors (NET). In NET, CXCR4 expression is associated with enhanced metastatic and invasive potential and worse prognosis but might be a theragnostic target. Likewise, activation of Wnt/β-catenin signaling may promote a more aggressive phenotype in NET. We hypothesized an interaction of the Wnt/β-catenin pathway with CXCR4 expression and function in NET. The NET cell lines BON-1, QGP-1, and MS-18 were exposed to Wnt inhibitors (5-aza-CdR, quercetin, and niclosamide) or the Wnt activator LiCl. The expressions of Wnt pathway genes and of CXCR4 were studied by qRT-PCR, Western blot, and immunohistochemistry. The effects of Wnt modulators on uptake of the CXCR4 ligand [\(^{68}\)Ga] Pentixafor were measured. The Wnt activator LiCl induced upregulation of CXCR4 and Wnt target gene expression. Treatment with the Wnt inhibitors had opposite effects. LiCl significantly increased [\(^{68}\)Ga] Pentixafor uptake, while treatment with Wnt inhibitors decreased radiopeptide uptake. Wnt pathway modulation influences CXCR4 expression and function in NET cell lines. Wnt modulation might be a tool to enhance the efficacy of CXCR4-directed therapies in NET or to inhibit CXCR4-dependent proliferative signaling. The underlying mechanisms for the interaction of the Wnt pathway with CXCR4 expression and function have yet to be clarified. KW - neuroendocrine tumor KW - NET KW - Wnt KW - β-catenin KW - CXCR4 KW - [\(^{68}\)Ga] Pentixafor KW - BON-1 KW - QGP-1 KW - MS-18 Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228914 SN - 2075-4418 VL - 11 IS - 2 ER - TY - JOUR A1 - Helfrich-Förster, C. A1 - Monecke, S. A1 - Spiousas, I. A1 - Hovestadt, T. A1 - Mitesser, O. A1 - Wehr, T. A. T1 - Women temporarily synchronize their menstrual cycles with the luminance and gravimetric cycles of the Moon JF - Science Advances N2 - Many species synchronize reproductive behavior with a particular phase of the lunar cycle to increase reproductive success. In humans, a lunar influence on reproductive behavior remains controversial, although the human menstrual cycle has a period close to that of the lunar cycle. Here, we analyzed long-term menstrual recordings of individual women with distinct methods for biological rhythm analysis. We show that women’s menstrual cycles with a period longer than 27 days were intermittently synchronous with the Moon’s luminance and/or gravimetric cycles. With age and upon exposure to artificial nocturnal light, menstrual cycles shortened and lost this synchrony. We hypothesize that in ancient times, human reproductive behavior was synchronous with the Moon but that our modern lifestyles have changed reproductive physiology and behavior. KW - moon KW - menstrual cycles Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231479 VL - 7 IS - 5 ER - TY - BOOK A1 - Alpermann, Björn T1 - Xinjiang - China und die Uiguren N2 - Die Situation in Chinas nordwestlicher Region Xinjiang hat in den letzten Jahren zunehmende internationale Aufmerksamkeit erfahren. Berichte über Masseninternierungen von Uiguren und anderen ethnischen Gruppen in Umerziehungslagern, Zwangsarbeit, Zwangssterilisation und weitere Menschenrechtsverletzungen beherrschen die Schlagzeilen und belasten die Beziehungen zwischen China und seinen Kritikern. Die chinesische Regierung rechtfertigt ihr Vorgehen hingegen als Kampf gegen Terrorismus, islamistischen Extremismus und ethnischen Separatismus. „Xinjiang – China und die Uiguren“ präsentiert erstmalig in deutscher Sprache eine tiefergehende wissenschaftliche Auseinandersetzung mit diesem kontroversen Thema. Prägnant und anschaulich führt der erste Teil des Buchs in die komplexe Geschichte der Region ein. Der zweite Teil stellt die Entwicklungen im 21. Jahrhundert dar. Hierbei zeigt sich ein facettenreiches Bild der sozioökonomischen Entwicklung, der ethnischen Identität sowie der Sprach- und Religionspolitik. Der dritte Teil hinterfragt die gängigen Deutungen des Xinjiang-Konflikts, analysiert Proteste und Terrorismus ebenso wie die staatlichen Repressionsmaßnahmen und die internationale Dimension der Auseinandersetzung. Quellennah, basierend auf den Ergebnissen der neuesten Forschung und in einem unaufgeregten Ton vermittelt „Xinjiang – China und die Uiguren“ ein ausgewogenes Bild der aktuellen Konflikte. KW - China KW - Uiguren KW - Xinijang KW - Geschichte KW - Konflikt KW - Sinkiang KW - Uiguren KW - Geschichte Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244128 SN - 978-3-95826-162-4 SN - 978-3-95826-163-1 N1 - Parallel erschienen als Druckausgabe in Würzburg University Press, 978-3-95826-162-4, 29,80 Euro. PB - Würzburg University Press CY - Würzburg ET - 1 ER -