@article{WiegeringRiedmeierThompsonetal.2022, author = {Wiegering, Verena and Riedmeier, Maria and Thompson, Lester D. R. and Virgone, Calogero and Redlich, Antje and Kuhlen, Michaela and Gultekin, Melis and Yalcin, Bilgehan and Decarolis, Boris and H{\"a}rtel, Christoph and Schlegel, Paul-Gerhardt and Fassnacht, Martin and Timmermann, Beate}, title = {Radiotherapy for pediatric adrenocortical carcinoma - Review of the literature}, series = {Clinical and Translational Radiation Oncology}, volume = {35}, journal = {Clinical and Translational Radiation Oncology}, doi = {10.1016/j.ctro.2022.05.003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300472}, pages = {56-63}, year = {2022}, abstract = {Background and purpose Pediatric adrenocortical carcinoma (pACC) is a rare disease with poor prognosis. Publications on radiotherapy (RT) are scarce. This review summarizes the current data on RT for pACC and possibly provides first evidence to justify its use in this setting. Materials and methods We searched the PubMed and Embase database for manuscripts regarding RT for pACC. Results We included 17 manuscripts reporting on 76 patients treated with RT, after screening 2961 references and 269 full articles. In addition, we added data of 4 unreported pACC patients treated by co-authors. All reports based on retrospective data. Median age at first diagnosis was 11.1 years (70\% female); 78\% of patients presented with hormonal activity. RT was mostly performed for curative intent (78\%). 88\% of RT were administered during primary therapy. The site of RT was predominantly the local tumor bed (76\%). Doses of RT ranged from 15 to 62 Gy (median 50 Gy). Information on target volumes or fractionation were lacking. Median follow-up was 6,9 years and 64\% of the patients died of disease, with 33\% alive without disease. In 16 of 48 patients with available follow-up data after adjuvant RT (33\%) no recurrence was reported and in 3 of 9 patients palliative RT seemed to induce some benefit for the patient. Conclusions Our first systematic review on RT for pACC provides too few data for any general recommendation, but adjuvant RT in patients with high risk might be considered. International collaborative studies are urgently needed to establish better evidence on the role of RT in this rare malignancy.}, language = {en} } @article{LoriniBescosAtinThavarajetal.2021, author = {Lorini, Luigi and Besc{\´o}s At{\´i}n, Coro and Thavaraj, Selvam and M{\"u}ller-Richter, Urs and Alberola Ferranti, Margarita and Pamias Romero, Jorge and S{\´a}ez Barba, Manel and de Pablo Garc{\´i}a-Cuenca, Alba and Bra{\~n}a Garc{\´i}a, Irene and Bossi, Paolo and Nuciforo, Paolo and Simonetti, Sara}, title = {Overview of oral potentially malignant disorders: from risk factors to specific therapies}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {15}, issn = {2072-6694}, doi = {10.3390/cancers13153696}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242779}, year = {2021}, abstract = {Oral squamous cell carcinoma (OSCC) is a very aggressive cancer, representing one of the most common malignancies worldwide. Oral potentially malignant disorders (OPMDs) regroup a variegate set of different histological lesions, characterized by the potential capacity to transform in OSCC. Most of the risk factors associated with OSCC are present also in OPMDs' development; however, the molecular mechanisms and steps of malignant transformation are still unknown. Treatment of OSCC, including surgery, systemic therapy and radiotherapy (alone or in combination), has suffered a dramatic change in last years, especially with the introduction of immunotherapy. However, most cases are diagnosed during the advanced stage of the disease, decreasing drastically the survival rate of the patients. Hence, early diagnosis of premalignant conditions (OPMDs) is a priority in oral cancer, as well as a massive education about risk factors, the understanding of mechanisms involved in malignant progression and the development of specific and more efficient therapies. The aim of this article is to review epidemiological, clinical, morphological and molecular features of OPMDs, with the purpose to lay the foundation for an exhaustive comprehension of these lesions and their ability of malignant transformation and for the development of more effective and personalized treatments.}, language = {en} } @article{DischingerHasingerKoenigsraineretal.2021, author = {Dischinger, Ulrich and Hasinger, Julia and K{\"o}nigsrainer, Malina and Corteville, Carolin and Otto, Christoph and Fassnacht, Martin and Hankir, Mohamed and Seyfried, Florian Johannes David}, title = {Toward a Medical Gastric Bypass: Chronic Feeding Studies With Liraglutide + PYY\(_{3-36}\) Combination Therapy in Diet-Induced Obese Rats}, series = {Frontiers in Endocrinology}, volume = {11}, journal = {Frontiers in Endocrinology}, issn = {1664-2392}, doi = {10.3389/fendo.2020.598843}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223113}, year = {2021}, abstract = {Background Combination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) have not been directly compared to Roux-en-Y gastric bypass (RYGB) in a standardized experimental setting. Methods High-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY\(_{3-36}\), (5) PYY\(_{3-36}\)+liraglutide (6), saline. Animals were kept on a free choice high- and low-fat diet. Food intake, preference, and body weight were measured daily for 4 weeks. Open field (OP) and elevated plus maze (EPM) tests were performed. Results RYGB reduced food intake and achieved sustained weight loss. Combined PYY\(_{3-36}\)+liraglutide treatment led to similar and plateaued weight loss compared to RYGB. Combined PYY\(_{3-36}\)+liraglutide treatment was superior to PYY\(_{3-36}\) (p ≤ 0.0001) and liraglutide (p ≤ 0.05 or p ≤ 0.01) mono-therapy. PYY\(_{3-36}\)+liraglutide treatment and RYGB also reduced overall food intake and (less pronounced) high-fat preference compared to controls. The animals showed no signs of abnormal behavior in OF or EPM. Conclusions Liraglutide and PYY\(_{3-36}\) combination therapy vastly mimics reduced food intake, food choice and weight reducing benefits of RYGB.}, language = {en} } @phdthesis{Kemmling2020, author = {Kemmling, Daniel}, title = {Parapneumonische Pleuraerg{\"u}sse (PPE) und Pleuraempyeme (PE) im Kindesalter: Einfluss des therapeutischen Managements auf den Krankheitsverlauf bei 994 Kindern und Jugendlichen in einer deutschlandweiten Surveillance-Studie}, doi = {10.25972/OPUS-19988}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199882}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Im Kindesalter treten bei etwa 1-2 \% der ambulant erworbenen Pneumonien parapneumonische Pleuraerg{\"u}sse (PPE) und Pleuraempyeme (PE) als lokale Komplikationen auf. F{\"u}r Deutschland liegen bisher nur wenige systematisch erhobene Daten zu Kindern und Jugendlichen mit PPE/PE vor. Ziele dieser Arbeit waren daher, die Charakteristika der p{\"a}diatrischen Patienten in Deutschland umfassend zu beschreiben sowie das diagnostische und therapeutische Management im Hinblick auf die aktuellen Empfehlungen zu analysieren. Zudem wird das Therapiemanagement von PPE/PE im Kindesalter aktuell kontrovers diskutiert. Dies betrifft insbesondere die invasiven Therapiemaßnahmen und den Zeitpunkt der jeweiligen Behandlungsoptionen bei schweren Krankheitsverl{\"a}ufen. Das Hauptziel dieser Arbeit war daher, den Krankheitsverlauf bei Kindern mit PPE/PE in Abh{\"a}ngigkeit von den initialen Therapiemaßnahmen zu vergleichen (Initiale Therapie: Behandlung mit h{\"o}chster Invasivit{\"a}t innerhalb von 3 Tagen nach Diagnosestellung). In dieser Arbeit wurden f{\"u}nf Jahre (Oktober 2010 bis Juni 2015) einer prospektiven, multizentrischen Surveillance-Studie ausgewertet, die in Zusammenarbeit mit der Erhebungseinheit seltener p{\"a}diatrischer Erkrankungen (ESPED) durchgef{\"u}hrt wurde. Insgesamt konnten 994 Kinder und Jugendliche mit PPE/PE in die Auswertungen eingeschlossen werden. Die lange Hospitalisationsdauer von 17 Tagen (IQR 13-24), die hohe Rate an intensivstation{\"a}ren Behandlungen (61\%) {\"u}ber eine Dauer von 7 Tagen (IQR 3-14) und die lange Ergussdauer von 14 Tagen (IQR 9-21) best{\"a}tigen, dass PPE/PE im Kindesalter schwerwiegende Erkrankungen sind. Bei allen Patienten erfolgte die Diagnosestellung mittels eines bildgebenden Verfahrens. Die hohe Rate von >99\% best{\"a}tigt den Einsatz eines R{\"o}ntgen-Thorax als bildgebendes Prim{\"a}rverfahren bei Kindern mit Pneumonie und entsprechend der nationalen und internationalen Empfehlungen, wurde eine Sonographie als Mittel der Wahl zur Diagnosestellung von PPE/PE eingesetzt. Der Einsatz einer Computertomographie bei {\"u}ber einem Drittel der 994 Kinder (34\%) erscheint dagegen sehr hoch. Dies gilt insbesondere f{\"u}r die Patienten im Alter von 13-17 Jahren, bei denen fast die H{\"a}lfte (47\%) per Computertomographie untersucht wurde. Alle 994 Kinder mit PPE/PE wurden nichtinvasiv behandelt. Eine zus{\"a}tzliche invasive Therapie mit Er{\"o}ffnung des Pleuraraumes wurde bei 789 (79\%) Patienten durchgef{\"u}hrt. Zur invasiven Behandlung wurde bei der H{\"a}lfte der Kinder eine Pleurapunktion (50\%), bei 70\% eine Pleuradrainage, sowie bei jeweils einem Viertel der Patienten eine intrapleurale Fibrinolyse (24\%) und/oder eine Operation (26\%) durchgef{\"u}hrt (Mehrfachnennungen m{\"o}glich). F{\"u}r eine erfolgreiche Behandlung von PPE/PE k{\"o}nnte insbesondere das initiale Therapiemanagement ausschlaggebend sein. Innerhalb von drei Tagen nach Diagnosestellung wurden 465 (46\%) der Kinder ausschließlich nichtinvasiv und 538 (54\%) zus{\"a}tzlichen invasiv behandelt (Pleurapunktion: n=94, 17\% von 538; Pleuradrainage: n=235, 44\%; Fibrinolyse: n=147, 27\%; Operation: n=62, 12\%). Invasive Folgeeingriffe waren bei einem Drittel der Patienten (34\%) notwendig. Deutschlandweit zeigten sich f{\"u}r das diagnostische und therapeutische Management von p{\"a}diatrischen PPE/PE eine große Heterogenit{\"a}t und bez{\"u}glich der initialen Maßnahmen eine teils starke Diskrepanz zu den aktuellen Empfehlungen. Insbesondere der zu h{\"a}ufige Einsatz einer Computertomographie zur bildgebenden Diagnostik und die bereits initial eingesetzten Therapiemaßnahmen mit hoher Invasivit{\"a}t sollten kritisch diskutiert werden. Zur Verbesserung des Behandlungsmanagements erscheint daher die Erstellung einer nationalen Leitlinie mit einem klaren, stadienadaptierten Behandlungsalgorithmus sehr sinnvoll. Die Vergleiche des Krankheitsverlaufs in Abh{\"a}ngigkeit von der initialen Therapie haben gezeigt, dass eine Vielzahl der Kinder mit PPE/PE erfolgreich mit einer alleinigen Antibiotikatherapie oder einer Antibiotika-Gabe mit zus{\"a}tzlicher Pleurapunktion bzw. Pleuradrainage behandelt werden k{\"o}nnen. Die kontrovers diskutierten Fragen, welche Kinder von einer initial invasiven Therapie profitieren und wann eine Therapiemaßnahme mit hoher Invasivit{\"a}t (intrapleurale Fibrinolyse oder Operation) erfolgen sollte, konnten anhand der hier dargestellten Ergebnisse nicht abschließend gekl{\"a}rt werden. Zur initialen Behandlung von PPE/PE sollte aufgrund der geringeren Invasivit{\"a}t eine Pleurapunktion bzw. eine Pleuradrainage mit m{\"o}glicher Fibrinolyse einem operativen Eingriff vorgezogen werden. Trotz der Schwere der Erkrankung, die h{\"a}ufig mit einer langwierigen Rekonvaleszenz verbunden ist, konnte in dieser großen Untersuchung mit 994 Kindern mit PPE/PE gezeigt werden, dass die Langzeitprognose von PPE/PE im Kindesalter unabh{\"a}ngig vom initialen Therapiemanagement als sehr gut einzusch{\"a}tzen ist und bleibende Folgesch{\"a}den (2\%) oder letale Krankheitsverl{\"a}ufe (1\%) sehr selten sind.}, subject = {Pleuraerguss}, language = {de} } @article{MemmelSisarioZoelleretal.2017, author = {Memmel, Simon and Sisario, Dmitri and Z{\"o}ller, Caren and Fiedler, Vanessa and Katzer, Astrid and Heiden, Robin and Becker, Nicholas and Eing, Lorenz and Ferreira, F{\´a}bio L.R. and Zimmermann, Heiko and Sauer, Markus and Flentje, Michael and Sukhorukov, Vladimir L. and Djuzenova, Cholpon S.}, title = {Migration pattern, actin cytoskeleton organization and response to PI3K-, mTOR-, and Hsp90-inhibition of glioblastoma cells with different invasive capacities}, series = {Oncotarget}, volume = {8}, journal = {Oncotarget}, number = {28}, doi = {10.18632/oncotarget.16847}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170719}, pages = {45298-45310}, year = {2017}, abstract = {High invasiveness and resistance to chemo- and radiotherapy of glioblastoma multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment strategies for preventing migration and invasion of GBM cells are needed. Using two different migration assays, Western blotting, conventional and super-resolution (dSTORM) fluorescence microscopy we examine the effects of the dual PI3K/mTOR-inhibitor PI-103 alone and in combination with the Hsp90 inhibitor NVP-AUY922 and/or irradiation on the migration, expression of marker proteins, focal adhesions and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19) markedly differing in their invasive capacity. Both lines were found to be strikingly different in morphology and migration behavior. The less invasive DK-MG cells maintained a polarized morphology and migrated in a directionally persistent manner, whereas the highly invasive SNB19 cells showed a multipolar morphology and migrated randomly. Interestingly, a single dose of 2 Gy accelerated wound closure in both cell lines without affecting their migration measured by single-cell tracking. PI-103 inhibited migration of DK-MG (p53 wt, PTEN wt) but not of SNB19 (p53 mut, PTEN mut) cells probably due to aberrant reactivation of the PI3K pathway in SNB19 cells treated with PI-103. In contrast, NVP-AUY922 exerted strong anti-migratory effects in both cell lines. Inhibition of cell migration was associated with massive morphological changes and reorganization of the actin cytoskeleton. Our results showed a cell line-specific response to PI3K/mTOR inhibition in terms of GBM cell motility. We conclude that anti-migratory agents warrant further preclinical investigation as potential therapeutics for treatment of GBM.}, language = {en} } @article{KingslakeDiasDawsonetal.2017, author = {Kingslake, Jonathan and Dias, Rebecca and Dawson, Gerard R. and Simon, Judit and Goodwin, Guy M. and Harmer, Catherine J. and Morriss, Richard and Brown, Susan and Guo, Boliang and Dourish, Colin T. and Ruh{\´e}, Henricus G. and Lever, Anne G. and Veltman, Dick J. and van Schaik, Anneke and Deckert, J{\"u}rgen and Reif, Andreas and St{\"a}blein, Michael and Menke, Andreas and Gorwood, Philip and Voegeli, G{\´e}raldine and Perez, Victor and Browning, Michael}, title = {The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial}, series = {Trials}, volume = {18}, journal = {Trials}, doi = {10.1186/s13063-017-2247-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173012}, year = {2017}, abstract = {Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4-6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient's antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50\% or greater decrease in baseline scores of depressionmeasured using the Quick Inventory of Depressive Symptoms - Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. Trial registration ClinicalTrials.gov, ID: NCT02790970. Registered on 30 March 2016.}, language = {en} } @article{WeidnerRousseauPlauthetal.2016, author = {Weidner, Christopher and Rousseau, Morten and Plauth, Annabell and Wowro, Sylvia J. and Fischer, Cornelius and Abdel-Aziz, Heba and Sauer, Sascha}, title = {Iberis amara Extract Induces Intracellular Formation of Reactive Oxygen Species and Inhibits Colon Cancer}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0152398}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167044}, pages = {e0152398}, year = {2016}, abstract = {Massively increasing global incidences of colorectal cancer require efficient treatment and prevention strategies. Here, we report unexpected anticancerogenic effects of hydroethanolic Iberis amara extract (IAE), which is known as a widely used phytomedical product for treating gastrointestinal complaints. IAE significantly inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC\(_{50}\)) of 6 and 9 μg/ml, respectively, and further generated inhibitory effects in PC-3 prostate and MCF7 breast cancer cells. Inhibition of proliferation in HT-29 cells was associated with a G2/M phase cell cycle arrest including reduced expression of various regulatory marker proteins. Notably, in HT-29 cells IAE further induced apoptosis by intracellular formation of reactive oxygen species (ROS). Consistent with predictions derived from our in vitro experiments, bidaily oral gavage of 50 mg/kg of IAE over 4 weeks resulted in significant inhibition of tumor growth in a mouse HT-29 tumor xenograft model. Taken together, Iberis amara extracts could become useful alternatives for preventing and treating the progression of colon cancer.}, language = {en} } @article{FilserDickMeyeretal.2015, author = {Filser, J{\"o}rg and Dick, Anke and Meyer, Thomas and Germer, Christoph-Thomas and von Rahden, Burkard H. A.}, title = {Peroral endoscopic myotomy for the treatment of achalasia in a 10-year-old male patient.}, series = {European Journal of Pediatric Surgery Reports}, volume = {3}, journal = {European Journal of Pediatric Surgery Reports}, number = {1}, doi = {10.1055/s-0034-1372461}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149502}, pages = {18-22}, year = {2015}, abstract = {Peroral endoscopic myotomy (POEM) is a new endoscopic treatment for achalasia with very good short-term results in adults. Data about POEM in pediatric patients are missing. We present the case of a 10-year-old male patient with type I (classic) achalasia, successfully treated with POEM. The procedure was accomplished in a similar fashion to the technique used in adults. Short-term results were fine, with a complete control of dysphagia and absence of reflux. We suggest that POEM is a suitable option in pediatric patients—similar to adults—but long-term results must be awaited.}, language = {en} } @article{WiedmannHeuschmannHermanek2015, author = {Wiedmann, Silke and Heuschmann, Peter U. and Hermanek, Peter}, title = {In reply: The quality of acute stroke treatment-an analysis of evidence-based indicators in 260 000 patients}, series = {Deutsches Aerzteblatt International}, volume = {112}, journal = {Deutsches Aerzteblatt International}, doi = {10.3238/arztebl.2015.0288b}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148666}, pages = {288}, year = {2015}, abstract = {No abstract available.}, language = {en} } @article{EiseleBlozikStoerketal.2013, author = {Eisele, Marion and Blozik, Eva and St{\"o}rk, Stefan and Tr{\"a}der, Jens-Martin and Herrmann-Lingen, Christoph and Scherer, Martin}, title = {Recognition of depression and anxiety and their association with quality of life, hospitalization and mortality in primary care patients with heart failure - study protocol of a longitudinal observation study}, series = {BMC Family Practice}, volume = {14}, journal = {BMC Family Practice}, number = {180}, issn = {1471-2296}, doi = {10.1186/1471-2296-14-180}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121881}, year = {2013}, abstract = {Background: International disease management guidelines recommend the regular assessment of depression and anxiety in heart failure patients. Currently there is little data on the effect of screening for depression and anxiety on the quality of life and the prognosis of heart failure (HF). We will investigate the association between the recognition of current depression/anxiety by the general practitioner (GP) and the quality of life and the patients' prognosis. Methods/Design: In this multicenter, prospective, observational study 3,950 patients with HF are recruited by general practices in Germany. The patients fill out questionnaires at baseline and 12-month follow-up. At baseline the GPs are interviewed regarding the somatic and psychological comorbidities of their patients. During the follow-up assessment, data on hospitalization and mortality are provided by the general practice. Based on baseline data, the patients are allocated into three observation groups: HF patients with depression and/or anxiety recognized by their GP (P+/+), those with depression and/or anxiety not recognized (P+/-) and patients without depression and/or anxiety (P-/-). We will perform multivariate regression models to investigate the influence of the recognition of depression and/or anxiety on quality of life at 12 month follow-up, as well as its influences on the prognosis (hospital admission, mortality). Discussion: We will display the frequency of GP-acknowledged depression and anxiety and the frequency of installed therapeutic strategies. We will also describe the frequency of depression and anxiety missed by the GP and the resulting treatment gap. Effects of correctly acknowledged and missed depression/anxiety on outcome, also in comparison to the outcome of subjects without depression/anxiety will be addressed. In case results suggest a treatment gap of depression/anxiety in patients with HF, the results of this study will provide methodological advice for the efficient planning of further interventional research.}, language = {en} }