@article{PatilGentschevAdelfingeretal.2012,
  author    = {Patil, Sandeep S. and Gentschev, Ivaylo and Adelfinger, Marion and Donat, Ulrike and Hess, Michael and Weibel, Stephanie and Nolte, Ingo and Frentzen, Alexa and Szalay, Aladar A.},
  title     = {Virotherapy of Canine Tumors with Oncolytic Vaccinia Virus GLV-1h109 Expressing an Anti-VEGF Single-Chain Antibody},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {10},
  doi       = {10.1371/journal.pone.0047472},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130039},
  pages     = {e47472},
  year      = {2012},
  abstract  = {Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor) single-chain antibody (scAb) GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 and the oncolytic and immunological effects of the GLV-1h109 vaccinia virus strain against canine soft tissue sarcoma and canine prostate carcinoma in xenograft models. Cell culture data demonstrated that the GLV-1h109 virus efficiently infect, replicate in and destroy both tested canine cancer cell lines. In addition, successful expression of GLAF-1 was demonstrated in virus-infected canine cancer cells and the antibody specifically recognized canine VEGF. In two different xenograft models, the systemic administration of the GLV-1h109 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice. Furthermore, tumor-specific virus infection led to a continued production of functional scAb GLAF-1, resulting in inhibition of angiogenesis. Overall, the GLV-1h109-mediated cancer therapy and production of immunotherapeutic anti-VEGF scAb may open the way for combination therapy concept i.e. vaccinia virus mediated oncolysis and intratumoral production of therapeutic drugs in canine cancer patients.},
  language  = {en}
}
@phdthesis{Kreissl2003,
  author    = {Kreißl, Michael},
  title     = {Vergleich der Wirksamkeit zweier verschieden dosierter Levothyroxin-Iodid-Kombinationen in der Therapie der euthyreoten diffusen Struma},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-6106},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {Grundproblematik und Fragestellung: In der Behandlung der endemischen Struma l{\"a}ßt sich durch Levothyroxin und/oder Iodid eine Reduktion des Schilddr{\"u}senvolumens erreichen. Eine unter Levothyroxintherapie auftretende TSH-Suppression kann sich jedoch {\"u}ber die Persistenz des intrathyreoidalen Iodmangels negativ auf die Rezidivh{\"a}ufigkeit auswirken. In dieser Studie soll die Wirksamkeit zweier verschieden dosierter Kombinationspr{\"a}parate aus Levothyroxin und Iodid verglichen werden, unter besonderer Ber{\"u}cksichtigung der Auswirkung des Levothyroxinanteils auf die intrathyreoidale Iodkonzentration. Patienten und Methodik: 44 Patientinnen mit euthyreoter diffuser Struma wurden in die Studie aufgenommen und randomisiert zwei Therapiegruppen zugeordnet. Gruppe A wurde mit 75 µg Levothyroxin und 150 µg Iodid (Verh{\"a}ltnis 1:2) behandelt. Gruppe B erhielt eine Kombination aus 100 µg Levothyroxin und 100 µg Iodid (Verh{\"a}ltnis 1:1) Die Therapie erstreckte sich {\"u}ber drei Monate mit anschließendem Beobachtungsintervall von drei Monaten ohne Medikation. Zu Studienbeginn, nach drei und sechs Monaten erfolgte eine Messung der intrathyreoidalen Iodkonzentration mittels R{\"o}ntgenfluoreszenzanalyse, des sonografischen Schilddr{\"u}senvolumens, der Iodausscheidung im Spontanurin und des basalen TSH, sowie der Schilddr{\"u}senhormone und des Thyreoglobulins. Die Vertr{\"a}glichkeit der Pr{\"a}parate wurde ebenfalls erfaßt. Ergebnisse: Im Verlauf der Studie, sowohl unter Therapie, als auch w{\"a}hrend der Nachbeobachtungsphase kam es in beiden Gruppen (auswertbar in Gruppe B n = 20, in Gruppe A n = 21) nur zu geringen, nicht signifikanten Ver{\"a}nderungen des intrathyreoidalen Iodgehalts. Durch die Behandlung reduzierte sich das Schilddr{\"u}senvolumen in Gruppe B um im Mittel 17,3\% gegen{\"u}ber dem Ausgangswert (p<0,001); in Gruppe A um 14,8\% (p<0,001). Der erreichte Effekt blieb in Gruppe B {\"u}ber die Nachbeobachtungsperiode erhalten, in Gruppe A sank das mittlere Volumen um weitere vier Prozent (n.s.). Ein signifikanter Unterschied zwischen den Gruppen ließ sich f{\"u}r die intrathyreoidale Iodkonzentration, wie auch f{\"u}r das Schilddr{\"u}senvolumen nicht nachweisen. In Gruppe B war eine statistisch signifikant st{\"a}rkere TSH-Suppression (p=0,04) und ein h{\"o}herer TSH-Anstieg (p=0,025) nach Therapie im Vergleich zu Gruppe A zu beobachten. Folgerung: Beide Kombinationspr{\"a}parate bewirkten eine vergleichbare dauerhafte Volumenreduktion der Schilddr{\"u}se ohne relevante Ver{\"a}nderung der intrathyreoidalen Iodkonzentration. Aufgrund des geringeren posttherapeutischen TSH-Anstiegs scheint die 1:2 Kombination gegen{\"u}ber der 1:1 Kombination geringe Vorteile zu bieten.},
  language  = {de}
}
@phdthesis{Kroeger2005,
  author    = {Kr{\"o}ger, Ute},
  title     = {Verfahrenswahl, Einflußfaktoren und Ergebnisse bei distaler Radiusfraktur unter besonderer Ber{\"u}cksichtigung der Plattenosteosynthese : eine retrospektive Studie anhand von 108 Patienten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-16132},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Retrospektive Studie mit dem Ziel, die Resultate nach offener Reposition und interner Fixation unter besonderer Ber{\"u}cksichtigung der Plattenosteosynthese bei distalen Radiusfrakturen zu dokumentieren und das Therapiekonzept durch Vergleich der Behandlungsindikation mit dem erreichten Ergebnis zu {\"u}berpr{\"u}fen. Vom 1.1.99 bis 31.12.00 wurden 108 Patienten mit distaler Radiusfraktur operativ versorgt,{\"u}berwiegend mit Plattenosteosynthese.Nach durchschnittlich 21 Monaten Beobachtung wurden 83 Patienten nachuntersucht, 58 davon waren operativ mit Plattenosteosynthese versorgt worden. Das mittlere Alter der plattenosteosynthetisch versorgten Patienten betrug 49,2 Jahre. Eingeteilt nach der AO-Klassifikation fanden sich 6 A2-, 8 A3-,1 B3-,3 C2- und 38 C3-Frakturen. Es zeigten sich durchschnittlich Palmarinklination 5°, Ulnarinklination 17,2°, Ulnavarianz 0,7mm, Bewegungsumfang im Mittel 53,7° Extension, 47,8°Flexion, 31,8°Ulnarduktion, 17,9°Radialduktion, 84,3°Supination und 89,8°Pronation. Die grobe Handkraft entsprach mit 29,1kg 83,1\% der kontralateralen Seite.Der DASH-Wert ergab 18,womit gute Alltagsfunktion widergespiegelt wurde. Nach traditionellem Handgelenkbewertungsschema(Mayo wrist score)ergaben sich bei den mit Plattenosteosynthese versorgten Patienten 71,6\% sehr gute, 7,5\% gute, 13,2\% befriedigende und 5,6\% schlechte Ergebnisse. Eine dauerhafte Retention der intraoperativ erzielten anatomiegerechten Gelenkstellung ließ sich bei 52\% der verplatteten Frakturen nachweisen, Redislokationen fanden sich {\"u}berwiegend in der dorsopalmaren Ebene. Die Augmentation von Beckenkammspongiosa hatte keinen entscheidenden Einfluß auf die Redislokationsrate. Komplikationsrate gering. Die Plattenosteosynthese ist f{\"u}r die anatomiegerechte Wiederherstellung des Handgelenkes ein wertvolles Therapieverfahren, da sie am ehesten die Retention der Fraktur realisieren kann. Mit winkelstabilen Platten-Systemen mit dem Vorteil des palmaren Zuganges und einer stabilen subchondralen Abst{\"u}tzung nach dem Fixateur interne-Prinzip ist eine exaktere Reposition und Retention auch bei intraartikul{\"a}ren Extensionsfrakturen ohne die Notwendigkeit einer Spongiosa-Plastik m{\"o}glich.},
  language  = {de}
}
@article{SchaeferWeibelDonatetal.2012,
  author    = {Sch{\"a}fer, Simon and Weibel, Stephanie and Donat, Ulrike and Zhang, Quian and Aguilar, Richard J. and Chen, Nanhai G. and Szalay, Aladar A.},
  title     = {Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors},
  series = {BMC Cancer},
  volume    = {12},
  journal   = {BMC Cancer},
  number    = {366},
  doi       = {10.1186/1471-2407-12-366},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140800},
  year      = {2012},
  abstract  = {Background Oncolytic viruses, including vaccinia virus (VACV), are a promising alternative to classical mono-cancer treatment methods such as surgery, chemo- or radiotherapy. However, combined therapeutic modalities may be more effective than mono-therapies. In this study, we enhanced the effectiveness of oncolytic virotherapy by matrix metalloproteinase (MMP-9)-mediated degradation of proteins of the tumoral extracellular matrix (ECM), leading to increased viral distribution within the tumors. Methods For this study, the oncolytic vaccinia virus GLV-1h255, containing the mmp-9 gene, was constructed and used to treat PC-3 tumor-bearing mice, achieving an intra-tumoral over-expression of MMP-9. The intra-tumoral MMP-9 content was quantified by immunohistochemistry in tumor sections. Therapeutic efficacy of GLV-1h255 was evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. Microenvironmental changes mediated by the intra-tumoral MMP-9 over-expression were investigated by microscopic quantification of the collagen IV content, the blood vessel density (BVD) and the analysis of lymph node metastasis formation. Results GLV-1h255-treatment of PC-3 tumors led to a significant over-expression of intra-tumoral MMP-9, accompanied by a marked decrease in collagen IV content in infected tumor areas, when compared to GLV-1h68-infected tumor areas. This led to considerably elevated virus titers in GLV-1h255 infected tumors, and to enhanced tumor regression. The analysis of the BVD, as well as the lumbar and renal lymph node volumes, revealed lower BVD and significantly smaller lymph nodes in both GLV-1h68- and GLV-1h255- injected mice compared to those injected with PBS, indicating that MMP-9 over-expression does not alter the metastasis-reducing effect of oncolytic VACV. Conclusions Taken together, these results indicate that a GLV-1h255-mediated intra-tumoral over-expression of MMP-9 leads to a degradation of collagen IV, facilitating intra-tumoral viral dissemination, and resulting in accelerated tumor regression. We propose that approaches which enhance the oncolytic effect by increasing the intra-tumoral viral load, may be an effective way to improve therapeutic outcome.},
  language  = {en}
}
@article{WalterReilichThieleetal.2013,
  author    = {Walter, Maggie C. and Reilich, Peter and Thiele, Simone and Schessl, Joachim and Schreiber, Herbert and Reiners, Karlheinz and Kress, Wolfram and M{\"u}ller-Reible, Clemens and Vorgerd, Matthias and Urban, Peter and Schrank, Bertold and Deschauer, Marcus and Schlotter-Weigel, Beate and Kohnen, Ralf and Lochm{\"u}ller, Hans},
  title     = {Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {8},
  journal   = {Orphanet Journal of Rare Diseases},
  number    = {26},
  issn      = {1750-1172},
  doi       = {10.1186/1750-1172-8-26},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125663},
  year      = {2013},
  abstract  = {Background: Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). Methods: We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences. Results: During one year of natural course, muscle strength declined about 2\% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects. Conclusion: Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis.},
  language  = {en}
}
@article{HeidrichCordesKlinkeretal.2015,
  author    = {Heidrich, Benjamin and Cordes, Hans-J{\"o}rg and Klinker, Hartwig and M{\"o}ller, Bernd and Naumann, Uwe and R{\"o}ssle, Martin and Kraus, Michael R. and B{\"o}ker, Klaus H. and Roggel, Christoph and Schuchmann, Marcus and Stoehr, Albrecht and Trein, Andreas and Hardtke, Svenja and Gonnermann, Andrea and Koch, Armin and Wedemeyer, Heiner and Manns, Michael P. and Cornberg, Markus},
  title     = {Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0128069},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151811},
  pages     = {e0128069},
  year      = {2015},
  abstract  = {Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80\%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 \(\mu\)g/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68\% [55\%; 81\%] in Group A and 57\% [43\%; 71\%] in Group B achieved SVR (p=0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70\%) was not met. In conclusion, approximately 23\% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group.},
  language  = {en}
}
@phdthesis{Slobodda2011,
  author    = {Slobodda, J{\"o}rg Thomas},
  title     = {Therapie des ziliolentikul{\"a}ren Blocks (malignen Glaukoms) nach intraokularer Chirurgie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-73520},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Therapie des malignen Glaukoms mittels Pars-Plana-Vitrektomie.},
  subject      = {Sekund{\"a}rglaukom},
  language  = {de}
}
@phdthesis{Maisch2012,
  author    = {Maisch, Kathrin},
  title     = {Therapie der Idiopathischen Lungenfibrose},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-79138},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Die idiopathische Lungenfibrose ist eine seltene Form der interstitiellen Lungenerkrankung mit variablem Krankheitsverlauf und schlechter Prognose. Diese Arbeit untersucht den Effekt einer Kombinationstherapie aus Immunsuppressiva (Azathioprin / Cyclophosphamid) und Corticosteroiden auf den Verlauf der Erkrankung, v. a. im Hinblick auf eine m{\"o}gliche Stabilisierung der Lungenfunktion.},
  subject      = {Lungenfibrose},
  language  = {de}
}
@article{HoppAlbertWeissenberger2015,
  author    = {Hopp, Sarah and Albert-Weissenberger, Christiane},
  title     = {The kallikrein-kinin system: a promising therapeutic target for traumatic brain injury},
  series = {Neural Regeneration Research},
  volume    = {10},
  journal   = {Neural Regeneration Research},
  number    = {6},
  doi       = {10.4103/1673-5374.158339},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149416},
  pages     = {885-886},
  year      = {2015},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{BeckerAndersenHofmeisterMuelleretal.2012,
  author    = {Becker, J{\"u}rgen C. and Andersen, Mads H. and Hofmeister-M{\"u}ller, Valeska and Wobser, Marion and Frey, Lidia and Sandig, Christiane and Walter, Steffen and Singh-Jasuja, Harpreet and K{\"a}mpgen, Eckhart and Opitz, Andreas and Zapatka, Marc and Br{\"o}cker, Eva-B. and thor Straten, Per and Schrama, David and Ugurel, Selma},
  title     = {Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma},
  series = {Cancer Immunology, Immunotherapy},
  volume    = {61},
  journal   = {Cancer Immunology, Immunotherapy},
  number    = {11},
  doi       = {10.1007/s00262-012-1266-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126215},
  pages     = {2091-2103},
  year      = {2012},
  abstract  = {Background Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets. Patients and methods This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS). Results Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen. Conclusion Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.},
  language  = {en}
}
@article{BeckerAndersenHofmeisterMuelleretal.2012,
  author    = {Becker, J{\"u}rgen C. and Andersen, Mads H. and Hofmeister-M{\"u}ller, Valeska and Wobser, Marion and Frey, Lidia and Sandig, Christiane and Walter, Steffen and Singh-Jasuja, Harpreet and K{\"a}mpgen, Eckhart and Opitz, Andreas and Zapatka, Marc and Br{\"o}cker, Eva-B. and thor Straten, Per and Schrama, David and Ugurel, Selma},
  title     = {Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma},
  series = {Cancer Immunology, Immunotherapy},
  volume    = {61},
  journal   = {Cancer Immunology, Immunotherapy},
  number    = {11},
  doi       = {10.1007/s00262-012-1266-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124830},
  pages     = {2091-2103},
  year      = {2012},
  abstract  = {Background Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets. Patients and methods This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS). Results Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen. Conclusion Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.},
  language  = {en}
}
@article{ZhangVanCrombruggenHoltappelsetal.2014,
  author    = {Zhang, Nan and Van Crombruggen, Koen and Holtappels, Gabriele and Lan, Feng and Katotomichelakis, Michail and Zhang, Luo and H{\"o}gger, Petra and Bachert, Claus},
  title     = {Suppression of Cytokine Release by Fluticasone Furoate vs. Mometasone Furoate in Human Nasal Tissue Ex-Vivo},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0093754},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116779},
  pages     = {e93754},
  year      = {2014},
  abstract  = {Background: Topical glucocorticosteroids are the first line therapy for airway inflammation. Modern compounds with higher efficacy have been developed, but head-to-head comparison studies are sparse. Objective: To compare the activity of two intranasal glucocorticoids, fluticasone furoate (FF) and mometasone furoate (MF) with respect to the inhibition of T helper (Th)1, Th2 and Th17 cytokine release in airway mucosa. Methods: We used an ex-vivo human nasal mucosal tissue model and employed pre-and post-Staphylococcus aureus enterotoxin B (SEB)-challenge incubations with various time intervals and drug concentrations to mimic typical clinical situations of preventive or therapeutic use. Results: At a fixed concentration of 10(-10) M, FF had significantly higher suppressive effects on interferon (IFN)-gamma,interleukin (IL)-2 and IL-17 release, but not IL-5 or tumor necrosis factor (TNF)-alpha, vs. MF. While the maximal suppressive activity was maintained when FF was added before or after tissue stimulation, the cytokine suppression capacity of MF appeared to be compromised when SEB-induced cell activation preceded the addition of the drug. In a pre-challenge incubation setting with removal of excess drug concentrations, MF approached inhibition of IL-5 and TNF-alpha after 6 and 24 hours while FF maximally blocked the release of these cytokines right after pre-incubation. Furthermore, FF suppressed a wider range of T helper cytokines compared to MF. Conclusion: The study demonstrates the potential of our human mucosal model and shows marked differences in the ability to suppress the release of various cytokines in pre-and post-challenge settings between FF and MF mimicking typical clinical situations of preventive or therapeutic use.},
  language  = {en}
}
@article{ArimanyNardiMinuesaPastorAngladaetal.2016,
  author    = {Arimany-Nardi, Cristina and Minuesa, Gerard and Pastor-Anglada, Mar{\c{c}}al and Keller, Thorsten and Erkizia, Itziar and Koepsell, Hermann and Martinez-Picado, Javier},
  title     = {Role of Human Organic Cation Transporter 1 (hOCT1) Polymorphisms in Lamivudine (3TC) Uptake and Drug-Drug Interactions},
  series = {Frontiers in Pharmacology},
  volume    = {7},
  journal   = {Frontiers in Pharmacology},
  number    = {175},
  doi       = {10.3389/fphar.2016.00175},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165236},
  year      = {2016},
  abstract  = {Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter extracellular loop (R61C and C88R). Drug-drug interaction measurements showed that co-administered drugs [abacavir (ABC), zidovudine (AZT), emtricitabine (FTC), tenofovir diproxil fumarate (TDF), efavirenz (EFV) and raltegravir (RAL)], differently inhibited 3TC uptake depending upon the polymorphic variant analyzed. These data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level.},
  language  = {en}
}
@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}
}
@phdthesis{Bauer2004,
  author    = {Bauer, Andrea},
  title     = {Prognostische und therapeutische Aspekte von Thymomen : eine retrospektive Studie von 582 F{\"a}llen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-12041},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Thymome sind seltene epitheliale Thymustumoren, die in der {\"u}berwiegenden Zahl der F{\"a}lle die F{\"a}higkeit zur Reifung und zum Export von T-Zellen behalten haben. Diese F{\"a}higkeit ist als Ursache f{\"u}r die h{\"a}ufige Asoziation dieser Tumoren mit Autoimmunph{\"a}nomenen (z.B Myasthenia gravis)anzunehmen. Die vorgelegte Studie zeigt die prognostische Relevanz der derzeit g{\"u}ltigen histologischen WHO-Klassifizierung von Thymomen. Das biologische Verhalten der einzelnen Thymomtypen korreliert dabei mit dem Ausmaß zytogenetischer Ver{\"a}nderungen. Wenige klinische und histologische Parameter wie der histologische Subtyp, Tumorstadium nach Masaoka sowie der Resektionsstatus reichen aus, um den Verlauf eines bestimmten Thymoms mit gen{\"u}gender Zuverl{\"a}ssigkeit prognostizieren zu k{\"o}nnen. Dies konnte in {\"U}bereinstimmung mit fr{\"u}heren Arbeiten in unserer Studie gezeigt werden. Somit m{\"u}ssen vor allem diese drei Parameter ber{\"u}cksichtigt werden, um eine ad{\"a}quate Therapie einleiten zu k{\"o}nnen. Angaben zu Alters- und Geschlechtsverteilung k{\"o}nnen diese Befunde erg{\"a}nzen, haben jedoch keine prognostische Signifikanz f{\"u}r die Wahl der Therapie. Die erhobenen Befunde der vorgelegten Follow-up Studie k{\"o}nnen als Grundlage prospektiver klinischer Therapiestudien dienen. Im Zentrum der Bem{\"u}hungen sollte hierbei nach unseren Ergebnissen die Therapie von „high-risk" Thymomen des Typ B und C stehen, bei denen eine prim{\"a}re vollst{\"a}ndige Resektion nicht m{\"o}glich ist, oder bei denen zum Zeitpunkt der Operation bereits Metastasen bestehen. Therapieoptionen mit multimodalen Therapiestrategien m{\"u}ssen daf{\"u}r noch weiter modifiziert und {\"u}ber l{\"a}ngere Zeitr{\"a}ume erprobt werden. Zudem sollten klinische Studien mit Somatostatin-Analoga als neue Therapiem{\"o}glichkeit gef{\"o}rdert werden. Aufgrund der {\"a}ußerst niedrigen Inzidenz von Thymomen und der niedrigen Frequenz von Patienten mit diesen ung{\"u}nstigen Thymomverl{\"a}ufen werden diese Versuche nationale oder internationale Bem{\"u}hungen erfordern.},
  language  = {de}
}
@phdthesis{Deeb2007,
  author    = {Deeb, Iyad},
  title     = {Periodische Proteinurie beim nephrotischen Syndrom - Konsequenzen f{\"u}r die Therapie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25804},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {In einer Beobachtungsstudie an 20 Patienten mit fokal sklerosierender und membran{\"o}ser Glomerulonephritis wurde der Effekt einer Therapie mit ACE- Hemmer, Methylprednisolon und Ciclosporin A {\"u}ber einen Zeitraum von bis zu 10 Jahren verfolgt. Die Effektivit{\"a}t der genannten Therapie ist in der Literatur gut dokumentiert. Die Studie beobachtet folgende neue, bislang nicht beschriebene Ergebnisse: 1. Das Ausmaß der Proteinurie beim nephrotischen Syndrom unterliegt einem 28-Tage-Zyklus. Als Arbeitshypothese nehmen wir zyklische Schwankungen in der Aktivit{\"a}t des Immunsystems an. 2. Die bislang g{\"a}ngige Praxis, das nephrotische Syndrom ein halbes Jahr lang oder allenfalls bis zur ersten Abnahme der Proteinurie zu therapieren bedarf einer Korrektur. Erst wenn die Periodizit{\"a}t der Proteinurie sistiert, kann die Therapie ausgeschlichen werden, ohne ein Rezidiv bef{\"u}rchten zu m{\"u}ssen. Auf jeden Fall muss wesentlich l{\"a}nger therapiert werden als gegenw{\"a}rtig in der Literatur berichtet. 3. Vor allem Patienten der Kategorie mit sehr langem Intervall zwischen Erstmanifestation und Therapiebeginn bed{\"u}rfen einer m{\"o}glicherweise lebenslangen Therapie um kein Endstage Renal Failure zu erleiden. 4. Das bislang g{\"u}ltige therapeutische Fenster der Ciclosporin-A-Therapie von 80 - 120 ng/ml Talspiegel kann bei gutem Ansprechen auf 60 - 80 ng/ml reduziert werden ohne hohes Rezidivrisiko.},
  subject      = {Proteinurie},
  language  = {de}
}
@article{FirdessaGoodAmstaldenetal.2015,
  author    = {Firdessa, Rebuma and Good, Liam and Amstalden, Maria Cecilia and Chindera, Kantaraja and Kamaruzzaman, Nor Fadhilah and Schultheis, Martina and R{\"o}ger, Bianca and Hecht, Nina and Oelschlaeger, Tobias A. and Meinel, Lorenz and L{\"u}hmann, Tessa and Moll, Heidrun},
  title     = {Pathogen- and host-directed antileishmanial effects mediated by polyhexanide (PHMB)},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {9},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {10},
  doi       = {10.1371/journal.pntd.0004041},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148162},
  pages     = {e0004041},
  year      = {2015},
  abstract  = {Background Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. Methodology/Principal Findings Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. Conclusions Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators.},
  language  = {en}
}
@article{Halbig Babu Gatter etal.2022,
  author    = {Halbig , Andreas and Babu , Sooraj K. and Gatter , Shirin and Latoschik , Marc Erich and Brukamp, Kirsten and von Mammen , Sebastian},
  title     = {Opportunities and challenges of Virtual Reality in healthcare - a domain experts inquiry},
  series = {Frontiers in Virtual Reality},
  volume    = {3},
  journal   = {Frontiers in Virtual Reality},
  issn      = {2673-4192},
  doi       = {10.3389/frvir.2022.837616},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284752},
  year      = {2022},
  abstract  = {In recent years, the applications and accessibility of Virtual Reality (VR) for the healthcare sector have continued to grow. However, so far, most VR applications are only relevant in research settings. Information about what healthcare professionals would need to independently integrate VR applications into their daily working routines is missing. The actual needs and concerns of the people who work in the healthcare sector are often disregarded in the development of VR applications, even though they are the ones who are supposed to use them in practice. By means of this study, we systematically involve health professionals in the development process of VR applications. In particular, we conducted an online survey with 102 healthcare professionals based on a video prototype which demonstrates a software platform that allows them to create and utilise VR experiences on their own. For this study, we adapted and extended the Technology Acceptance Model (TAM). The survey focused on the perceived usefulness and the ease of use of such a platform, as well as the attitude and ethical concerns the users might have. The results show a generally positive attitude toward such a software platform. The users can imagine various use cases in different health domains. However, the perceived usefulness is tied to the actual ease of use of the platform and sufficient support for learning and working with the platform. In the discussion, we explain how these results can be generalized to facilitate the integration of VR in healthcare practice.},
  language  = {en}
}
@article{WangChenMinevetal.2012,
  author    = {Wang, Huiqiang and Chen, Nanhai G. and Minev, Boris R. and Szalay, Aladar A.},
  title     = {Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells},
  series = {Journal of Translational Medicine},
  volume    = {10},
  journal   = {Journal of Translational Medicine},
  number    = {167},
  doi       = {10.1186/1479-5876-10-167},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130019},
  year      = {2012},
  abstract  = {Background: Recent data suggest that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are responsible for relapses after apparently curative therapies have been undertaken. Hence, novel cancer therapies will be needed to test for both tumor regression and CSC targeting. The use of oncolytic vaccinia virus (VACV) represents an attractive anti-tumor approach and is currently under evaluation in clinical trials. The purpose of this study was to demonstrate whether VACV does kill CSCs that are resistant to irradiation and chemotherapy. Methods: Cancer stem-like cells were identified and separated from the human breast cancer cell line GI-101A by virtue of increased aldehyde dehydrogenase 1 (ALDH1) activity as assessed by the ALDEFLUOR assay and cancer stem cell-like features such as chemo-resistance, irradiation-resistance and tumor-initiating were confirmed in cell culture and in animal models. VACV treatments were applied to both ALDEFLUOR-positive cells in cell culture and in xenograft tumors derived from these cells. Moreover, we identified and isolated CD44\(^+\)CD24\(^+\)ESA\(^+\) cells from GI-101A upon an epithelial-mesenchymal transition (EMT). These cells were similarly characterized both in cell culture and in animal models. Results: We demonstrated for the first time that the oncolytic VACV GLV-1h68 strain replicated more efficiently in cells with higher ALDH1 activity that possessed stem cell-like features than in cells with lower ALDH1 activity. GLV-1h68 selectively colonized and eventually eradicated xenograft tumors originating from cells with higher ALDH1 activity. Furthermore, GLV-1h68 also showed preferential replication in CD44\(^+\)CD24\(^+\)ESA\(^+\) cells derived from GI-101A upon an EMT induction as well as in xenograft tumors originating from these cells that were more tumorigenic than CD44\(^+\)CD24\(^-\)ESA\(^+\) cells. Conclusions: Taken together, our findings indicate that GLV-1h68 efficiently replicates and kills cancer stem-like cells. Thus, GLV-1h68 may become a promising agent for eradicating both primary and metastatic tumors, especially tumors harboring cancer stem-like cells that are resistant to chemo and/or radiotherapy and may be responsible for recurrence of tumors.},
  language  = {en}
}
@article{WeilandBeezWestermaieretal.2021,
  author    = {Weiland, Judith and Beez, Alexandra and Westermaier, Thomas and Kunze, Ekkehard and Sir{\´e}n, Anna-Leena and Lilla, Nadine},
  title     = {Neuroprotective strategies in aneurysmal subarachnoid hemorrhage (aSAH)},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {11},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22115442},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260755},
  year      = {2021},
  abstract  = {Aneurysmal subarachnoid hemorrhage (aSAH) remains a disease with high mortality and morbidity. Since treating vasospasm has not inevitably led to an improvement in outcome, the actual emphasis is on finding neuroprotective therapies in the early phase following aSAH to prevent secondary brain injury in the later phase of disease. Within the early phase, neuroinflammation, thromboinflammation, disturbances in brain metabolism and early neuroprotective therapies directed against delayed cerebral ischemia (DCI) came into focus. Herein, the role of neuroinflammation, thromboinflammation and metabolism in aSAH is depicted. Potential neuroprotective strategies regarding neuroinflammation target microglia activation, metalloproteases, autophagy and the pathway via Toll-like receptor 4 (TLR4), high mobility group box 1 (HMGB1), NF-κB and finally the release of cytokines like TNFα or IL-1. Following the link to thromboinflammation, potential neuroprotective therapies try to target microthrombus formation, platelets and platelet receptors as well as clot clearance and immune cell infiltration. Potential neuroprotective strategies regarding metabolism try to re-balance the mismatch of energy need and supply following aSAH, for example, in restoring fuel to the TCA cycle or bypassing distinct energy pathways. Overall, this review addresses current neuroprotective strategies in aSAH, hopefully leading to future translational therapy options to prevent secondary brain injury.},
  language  = {en}
}
@article{KesslerFeldheimSchmittetal.2020,
  author    = {Kessler, Almuth F. and Feldheim, Jonas and Schmitt, Dominik and Feldheim, Julia J. and Monoranu, Camelia M. and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten},
  title     = {Monopolar Spindle 1 Kinase (MPS1/TTK) mRNA Expression is Associated with Earlier Development of Clinical Symptoms, Tumor Aggressiveness and Survival of Glioma Patients},
  series = {Biomedicines},
  volume    = {8},
  journal   = {Biomedicines},
  number    = {7},
  doi       = {10.3390/biomedicines8070192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236105},
  year      = {2020},
  abstract  = {Inhibition of the protein kinase MPS1, a mitotic spindle-checkpoint regulator, reinforces the effects of multiple therapies against glioblastoma multiforme (GBM) in experimental settings. We analyzed MPS1 mRNA-expression in gliomas WHO grade II, III and in clinical subgroups of GBM. Data were obtained by qPCR analysis of tumor and healthy brain specimens and correlated with the patients' clinical data. MPS1 was overexpressed in all gliomas on an mRNA level (ANOVA, p < 0.01) and correlated with tumor aggressiveness. We explain previously published conflicting results on survival: high MPS1 was associated with poorer long term survival when all gliomas were analyzed combined in one group (Cox regression: t < 24 months, p = 0.009, Hazard ratio: 8.0, 95\% CI: 1.7-38.4), with poorer survival solely in low-grade gliomas (LogRank: p = 0.02, Cox regression: p = 0.06, Hazard-Ratio: 8.0, 95\% CI: 0.9-66.7), but not in GBM (LogRank: p > 0.05). This might be due to their lower tumor volume at the therapy start. GBM patients with high MPS1 mRNA-expression developed clinical symptoms at an earlier stage. This, however, did not benefit their overall survival, most likely due to the more aggressive tumor growth. Since MPS1 mRNA-expression in gliomas was enhanced with increasing tumor aggressiveness, patients with the worst outcome might benefit best from a treatment directed against MPS1.},
  language  = {en}
}
@article{KienleGarridoBreitenbachChudejetal.2018,
  author    = {Kienle-Garrido, Melina-Lor{\´e}n and Breitenbach, Tim and Chudej, Kurt and Borz{\`i}, Alfio},
  title     = {Modeling and numerical solution of a cancer therapy optimal control problem},
  series = {Applied Mathematics},
  volume    = {9},
  journal   = {Applied Mathematics},
  number    = {8},
  doi       = {10.4236/am.2018.98067},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177152},
  pages     = {985-1004},
  year      = {2018},
  abstract  = {A mathematical optimal-control tumor therapy framework consisting of radio- and anti-angiogenesis control strategies that are included in a tumor growth model is investigated. The governing system, resulting from the combination of two well established models, represents the differential constraint of a non-smooth optimal control problem that aims at reducing the volume of the tumor while keeping the radio- and anti-angiogenesis chemical dosage to a minimum. Existence of optimal solutions is proved and necessary conditions are formulated in terms of the Pontryagin maximum principle. Based on this principle, a so-called sequential quadratic Hamiltonian (SQH) method is discussed and benchmarked with an "interior point optimizer―a mathematical programming language" (IPOPT-AMPL) algorithm. Results of numerical experiments are presented that successfully validate the SQH solution scheme. Further, it is shown how to choose the optimisation weights in order to obtain treatment functions that successfully reduce the tumor volume to zero.},
  language  = {en}
}
@phdthesis{Riedel2001,
  author    = {Riedel, Walter K.},
  title     = {Metastasierungsverhalten von Mundh{\"o}hlenkarzinomen in Abh{\"a}ngigkeit vom Therapieregime},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1181791},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2001},
  abstract  = {In der vorliegenden retrospektiven Studie wurde das Metastasierungsverhalten von Mundh{\"o}hlenkarzinomen des Krankengutes der Klinik und Poliklinik f{\"u}r Mund-, Kiefer- und Gesichtschirurgie der Universit{\"a}t W{\"u}rzburg aus den Jahren 1985 bis 1999 bei unterschiedlichen Therapiekonzepten untersucht. 774 Patienten wurden in die Untersuchung einbezogen. Das Durchschnittsalter der Patienten betrug 59 Jahre. Das Verh{\"a}ltnis von m{\"a}nnlichen zu weiblichen Patienten lag bei 4:1. 36,3 Prozent (280) der Tumoren lagen im Bereich des Mundbodens, 15,9 Prozent (123) in der Unterlippe, 13,7 Prozent (106) im Bereich des Oropharynx, 12,4 Prozent (96) im Unterkiefer-Alveolarfortsatz, 10,2 Prozent (79) in der Zunge, 7,1 Prozent (55) in Oberkiefer und Gaumen, 3,1 Prozent (24) in der Wangenschleimhaut und 1,2 Prozent (9) in der Oberlippe. Eine alleinige chirurgische Tumorresektion wurde bei 60,1 Prozent (465) der Patienten durchgef{\"u}hrt. Eine chirurgische Therapie mit pr{\"a}operative Radiatio (40 Gy) erhielten 1,3 Prozent (10) der Patienten, eine chirurgische Therapie mit kombinierter pr{\"a}operativer Radio-Chemo-Therapie (40 Gy) erhielten 25,5 Prozent (197). 7,4 Prozent (57) der Patienten erhielten eine alleinige Radio-Chemo-Therapie, 4,9 Prozent (38) eine Radiatio solo. Postoperativ wurde eine Bestrahlung bei 5,0 Prozent (39) und eine Chemotherapie bei 0,3 Prozent (2) der Patienten durchgef{\"u}hrt. 21,0 Prozent (163) aller Patienten erhielten eine ipsilaterale Lymphknotenausr{\"a}umung, 22,4 Prozent (173) eine bilaterale Lymphbahnausr{\"a}umung. 50,6 Prozent (170) der Patienten, deren Halsweichteile ausger{\"a}umt wurden, erhielten ipsilateral eine radikale Neck dissection, 21,4 Prozent (72) eine konservierende Neck dissection, 28,0 Prozent (94) eine suprahyoidale Ausr{\"a}umung. 72,5 Prozent (561) der Patienten blieben innerhalb der Nachbeobachtungszeit (durchschnittlich 2,9 Jahre) rezidiv- bzw. metastasenfrei. Ein Lokalrezidiv entwickelten 14,9 Prozent (115) der Patienten. Metastasen entwickelten innerhalb der Nachbeobachtungszeit 16,5 Prozent (128) der Patienten: 68,8 Prozent (88) region{\"a}re Metastasen, 31,2 Prozent (40) Fernmetastasen. Einen statistisch signifikanten Einfluss (p<0,05) auf die Metastasenh{\"a}ufigkeit hatte die Lokalisation des Prim{\"a}rtumors (26,3 Prozent Metastasen bei Tumoren im Bereich der Wangenschleimhaut, 24,3 Prozent bei Mundbodenkarzinomen, 23,6 Prozent bei Oropharynxkarzinomen, 20,0 Prozent bei Oberkieferkarzinomen, 15,9 Prozent bei Zungenkarzinomen, 13,4 Prozent bei Karzinomen des Unterkiefer-Alveolarfortsatzes, 7,0 Prozent bei Lippenkarzinomen und 0,0 Prozent Metastasen bei Oberlippenkarzinomen). Wurde eine alleinige Tumorresektion durchgef{\"u}hrt, traten bei 9,7 Prozent der Patienten Metastasen auf. Wurde die Behandlung durch eine pr{\"a}operative Radio-Chemo-Therapie erweitert, traten bei 35,0 Prozent der Patienten Metastasen auf. Wurde zus{\"a}tzlich noch eine postoperative Radiatio durchgef{\"u}hrt, entwickelten 38,5 Prozent der Patienten Metastasen. Nach Durchf{\"u}hrung einer alleinigen Radiatio mit 70 Gy traten bei 11,1 Prozent der Patienten Metastasen auf, nach kombinierter Radio-Chemo-Therapie (70 Gy) bei 20,5 Prozent der Patienten. Histologisch positive Resekatr{\"a}nder erh{\"o}hten die Metastasenwahrscheinlichkeit statistisch signifikant von 17,0 Prozent auf 45,7 Prozent. Von der Art der Lymphbahnausr{\"a}umung (ohne Ber{\"u}cksichtigung adjuvanter Therapien) ist die Metastasenwahrscheinlichkeit statistisch signifikant abh{\"a}ngig. Nach Durchf{\"u}hrung einer alleinigen ipsilateralen radikalen Neck dissection zeigte sich eine Metastasierungsrate von 25,6 Prozent. Wurde statt dessen eine konservierende Neck dissection durchgef{\"u}hrt, traten bei 40,0 Prozent der Patienten Metastasen auf. Wurde die ipsilaterale radikale Neck dissection mit einer kontralateralen suprahyoidalen Ausr{\"a}umung kombiniert, traten bei 37,1 Prozent der Patienten Metastasen auf. Nach ipsilateraler konservierender Neck dissection und kontralateraler suprahyoidaler Ausr{\"a}umung zeigten sich bei 55,3 Prozent der Patienten Metastasen. Die Inzidenz kontralateraler Metastasen lag bei alleiniger ipsilateraler Behandlung bei 34,3 Prozent, bei zus{\"a}tzlicher kontralateraler suprahyoidaler Ausr{\"a}umung bei 30,2 Prozent (trotz der hier zumeist vorliegenden ung{\"u}nstigeren Prognose durch gr{\"o}ßere Prim{\"a}rtumoren oder deren Lage im Bereich der K{\"o}rpermedianen).},
  language  = {de}
}
@article{BenoitGoebeler2015,
  author    = {Benoit, Sandrine and Goebeler, Matthias},
  title     = {Mepacrine in recalcitrant cutaneous lupus erythematosus: old-fashioned or still useful?},
  series = {Acta Dermato-Venereologica},
  volume    = {95},
  journal   = {Acta Dermato-Venereologica},
  doi       = {10.2340/00015555-2031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149181},
  pages     = {596-599},
  year      = {2015},
  abstract  = {Treatment of recalcitrant cutaneous lupus erythematosus (CLE) is challenging. In situations where conventional treatment approaches fail mepacrine - an antimalarial/antiinfiammatory drug that has fallen into oblivion in the last decades might still be a promising option. We retrospectively analysed medical records of 10 patients with refractory CLE that were treated with mepacrine (100-200 mg/day) as mono- or combination therapy for various time intervals between 2001 and 2013 at the University Hospital Wurzburg. Mepacrine was generally well tolerated. Side effects were mild and usually resolved after reduction or cessation. Over 50\% of the patients experienced amelioration of their symptoms despite a previously recalcitrant clinical course. Altogether, our data demonstrate that mepacrine still remains a useful and effective therapeutic option for otherwise treatment-resistant CLE.},
  language  = {en}
}
@phdthesis{Fobbe2009,
  author    = {Fobbe, Alexandra},
  title     = {Lokalisation, klinische und r{\"o}ntgenologische Symptomatik sowie Therapie bei Patienten mit follikul{\"a}ren Zysten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-35663},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {Die Basis der vorliegenden retrospektiven Auswertung bilden die Krankenunterlagen von 90 Patienten, die im Zeitraum von 1995 bis 2004 in der Klinik und Poliklinik f{\"u}r Mund-, Kiefer- und Gesichtschirurgie der Universit{\"a}t W{\"u}rzburg wegen einer follikul{\"a}ren Zyste im Ober- oder Unterkiefer ambulant und station{\"a}r behandelt wurden. In dieser statistischen Auswertung wird deutlich, dass follikul{\"a}re Zysten vermehrt bei dem m{\"a}nnlichen Patientengut aufgetreten sind. Das Haupterkrankungsalter lag zwischen dem 31. und 50. Lebensjahr. Die retrospektive Analyse der Krankenakten zeigt, dass die follikul{\"a}ren Zysten vermehrt im Unterkiefer lokalisiert waren. Die unteren Weisheitsz{\"a}hne waren am h{\"a}ufigsten betroffen. Bez{\"u}glich des Therapiekonzeptes war die Zystektomie mit Zahnentfernung das am h{\"a}ufigsten durchgef{\"u}hrte. F{\"u}r die Zystenhohlraumauff{\"u}llung werden diverse M{\"o}glichkeiten angesprochen. Intraoperative Komplikationen kamen nur selten vor. Bei den postoperativen Komplikationen wurden die entz{\"u}ndlichen postoperativen Komplikationen eigens betrachtet. Als relevante entz{\"u}ndliche Komplikation wurde die Infektion dokumentiert. Zus{\"a}tzlich werden die Ergebnisse mit zahlreichen Publikationen verglichen.},
  subject      = {Therapie},
  language  = {de}
}
@article{KraemerBijnensStoerketal.2015,
  author    = {Kr{\"a}mer, Johannes and Bijnens, Bart and St{\"o}rk, Stefan and Ritter, Christian O. and Liu, Dan and Ertl, Georg and Wanner, Christoph and Weidemann, Frank},
  title     = {Left ventricular geometry and blood pressure as predictors of adverse progression of Fabry cardiomyopathy},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {11},
  doi       = {10.1371/journal.pone.0140627},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145131},
  pages     = {e0140627},
  year      = {2015},
  abstract  = {Background In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated. Methods In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed. Results Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2\% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05). Conclusions LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy.},
  language  = {en}
}
@phdthesis{Fremerey2002,
  author    = {Fremerey, Christian},
  title     = {Krankheitslast des Hypoparathyreoidismus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-4578},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {Patienten mit einem Hypoparathyreoidismus (HP) sind durch die Unterfunktion der Nebenschilddr{\"u}sen und den resultierenden Mangel an Parathormon (PTH) nicht in der Lage, einen ausreichenden Serum-Calcium-Spiegel aufrecht zu erhalten. Die aktuelle Therapie umfasst die Substitution von Calcium und Vitamin D, als Therapiekontrolle dient der Serum-Calcium-Wert. Erfahrungen aus der Betreuung der Patienten legen jedoch den Verdacht nahe, dass es damit nicht m{\"o}glich ist, eine ausreichende Beschwerdefreiheit zu erlangen. In der vorliegenden Studie wurden insgesamt 29 Patienten (28 Frauen, 1 Mann) untersucht, die als Folge einer Operation an einem HP erkrankt sind oder bei denen ein idiopathischer oder Pseudo-HP besteht. 25 Patientinnen wurden mit einer Kontrollgruppe von 25 Schilddr{\"u}senoperierten verglichen, bei denen es postoperativ nicht zur Ausbildung eines HP gekommen war. Mit Beschwerdeinventaren wurden Befindlichkeitsst{\"o}rungen quantifiziert und anhand von Nierensonographie, Osteodensitometrie und augen{\"a}rztlicher Untersuchung nach k{\"o}rperlichen Manifestationen gesucht. In den Beschwerdeinventaren zeigte sich bei den Patientinnen im Vergleich zur Kontrollgruppe eine signifikant erh{\"o}hte generelle Beschwerdelast (SCL 90-R: p=0.02, B-L: p=0.002, GBB-24: p=0.011) und eine signifikant st{\"a}rkere Auspr{\"a}gung von Somatisierungsneigung (p=0.032), Depressivit{\"a}t (p=0.016), {\"A}ngstlichkeit (p=0.001) und Phobie (p=0.017). Sonographisch konnte bei zwei Patientinnen eine Nephrokalzinose nachgewiesen werden. Die negative Korrelation von Serum-Calcium und Serum-Phosphat bei der Patientengruppe (r=-0.42, p=0.035) sprach jedoch f{\"u}r ein erh{\"o}htes Verkalkungsrisiko. Die Osteodensitometrie mittels DXA ergab im Vergleich zum Normkollektiv eine signifikant erh{\"o}hte Knochendichte an der Lendenwirbels{\"a}ule (p=0.0005) und den Messpunkten des proximalen Femurs (Hals: p=0.015, Trochanter: p<0.0001). Die Messung mit pQCT am Radius zeigte keinen signifikanten Unterschied (Gesamt: p=0.32, Spongiosa: p=0.28). Die augen{\"a}rztliche Untersuchung ergab eine Katarakth{\"a}ufigkeit von 55\% bei den untersuchten Patienten, 40\% davon hatten kortikale Tr{\"u}bungen. Die Ergebnisse zeigen, dass es mit der heute durchgef{\"u}hrten alleinigen Substitution von Calcium und Vitamin D nicht gelingt, Patienten mit HP zufriedenstellend zu therapieren. Trotz guter Einstellung des Serum-Calciums bestehen sowohl funktionelle als auch strukturelle St{\"o}rungen. Die vorliegende Studie belegt die Notwendigkeit der weiteren Erforschung von kausalen Therapieans{\"a}tzen wie der Transplantation von NSD-Gewebe und der Substitution von PTH.},
  language  = {de}
}
@phdthesis{Reiter2011,
  author    = {Reiter, Andrea},
  title     = {Irrer lugt ins Land - {\"U}ber 'Irre' und den Umgang mit Ihnen am Ende des 18. Jahrhunderts am Beispiel der N{\"u}rnberger Gesellschaft},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71939},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Die Situation der Psychiatrie und die institutionelle Unterbringung der Geisteskranken am Ende des 18. Jahrhunderts sind gut erforscht. Doch was dem einzelnen Geisteskranken widerfuhr, unter welchen Sorgen und N{\"o}ten er als Kranker und Patient litt, welchen Problemen seine Familie und sein Umfeld ausgesetzt waren, wie es ihm außerhalb der Anstalt erging und welche Faktoren zur Unterbringung in eine Anstalt oder in einem Gef{\"a}ngnis oder auch zur Entlassung aus diesen beitrugen, ist bisher nur wenig erforscht. Der hier behandelte Aktenbestand des N{\"u}rnberger Stadtarchivs l{\"a}sst Einblicke in den medizinischen, amtlichen und privaten Umgang mit den Irren am Ende des 18. Jahrhunderts zu. Die Irren in N{\"u}rnberg und Umgebung wurden zun{\"a}chst meist von Angeh{\"o}rigen betreut und versorgt, wobei diese Aufgabe mit nicht wenigen Problemen behaftet war. Neben der finanziellen Belastung konnte ein Irrer auch zur Gefahr f{\"u}r Leib und Leben werden, wenn er in einem Anfall von Raserei gewaltt{\"a}tig gegen sich und andere wurde. In solchen F{\"a}llen ließ man bis zur Anzeige im Sch{\"o}ffenamt mit der Bitte, den Betroffenen internieren zu d{\"u}rfen, keine Zeit verstreichen. Die Meinungen der Amts{\"a}rzte bzgl. der Internierungspraxis unterschieden sich hier ganz offensichtlich voneinander. W{\"a}hrend die Betroffenen in den Akten bis etwa 1789 vorwiegend aufgrund von ‚Raserei', ‚Faulheit' oder ‚Bl{\"o}dheit' angezeigt und meist eine Bestrafung in Form von k{\"o}rperlicher Z{\"u}chtigung oder Freiheitsberaubung gefordert wurde, so {\"a}nderte der Umgang mit den Irren merklich. Internierungen gerieten mehr und mehr in die Kritik, wurden zu einer {\"U}bergangs- und sp{\"a}ter zu einer Art ‚Notl{\"o}sung'. Der mythisch-mystische Aspekt der Geisteskrankheiten geriet zunehmend in den Hintergrund. Viele Angeh{\"o}rige k{\"u}mmerten sich auch ohne Weisung des Amtsarztes f{\"u}rsorglich um ein irres Familienmitglied, bis es, z. B. aufgrund von Geldn{\"o}ten, zur Internierung kam. Dr. Preu versuchte gerade die finanzielle Belastung der Familien, die ein wahnsinniges Familienmitglied betreuten, zu reduzieren. Seine Bem{\"u}hungen f{\"u}r einen sozial-integrativen Umgang mit den Irren zeigten auch, dass man das Wegsperren der Wahnsinnigen zunehmend ablehnte und deren Reintegration f{\"o}rderte. Anhand von lebendigen Beispielen wird dieser Wandel in der Abhandlung anschaulich dargestellt.},
  subject      = {Irrer},
  language  = {de}
}
@article{KleinschnitzNiemczykRehbergWeberetal.2015,
  author    = {Kleinschnitz, Christoph and Niemczyk, Gabriele and Rehberg-Weber, Karin and Wernsd{\"o}rfer, Colin},
  title     = {Interferon Beta-1a (AVONEX®) as a treatment option for untreated patients with multiple sclerosis (AXIOM): a prospective, observational study},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms160715271},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148487},
  pages     = {15271-15286},
  year      = {2015},
  abstract  = {The efficacy and safety of first-line disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM) trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a) after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection-related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies.},
  language  = {en}
}
@article{HetzAcikgoezVossetal.2014,
  author    = {Hetz, Susan and Acikgoez, Ali and Voss, Ulrike and Nieber, Karen and Holland, Heidrun and Hegewald, Cindy and Till, Holger and Metzger, Roman and Metzger, Marco},
  title     = {In Vivo Transplantation of Neurosphere-Like Bodies Derived from the Human Postnatal and Adult Enteric Nervous System: A Pilot Study},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0093605},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116793},
  pages     = {e93605},
  year      = {2014},
  abstract  = {Recent advances in the in vitro characterization of human adult enteric neural progenitor cells have opened new possibilities for cell-based therapies in gastrointestinal motility disorders. However, whether these cells are able to integrate within an in vivo gut environment is still unclear. In this study, we transplanted neural progenitor-containing neurosphere-like bodies (NLBs) in a mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived cell types and functional improvement. NLBs were propagated from postnatal and adult human gut tissues. Cells were characterized by immunohistochemistry, quantitative PCR and subtelomere fluorescence in situ hybridization (FISH). For in vivo evaluation, the plexus of murine colon was damaged by the application of cationic surfactant benzalkonium chloride which was followed by the transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells were visualized by combined in situ hybridization (Alu) and immunohistochemistry (PGP9.5, GFAP, SMA). In addition, we determined nitric oxide synthase (NOS)-positive neurons and measured hypertrophic effects in the ENS and musculature. Contractility of treated guts was assessed in organ bath after electrical field stimulation. NLBs could be reproducibly generated without any signs of chromosomal alterations using subtelomere FISH. NLB-derived cells integrated within the host tissue and showed expected differentiated phenotypes i.e. enteric neurons, glia and smooth muscle-like cells following in vivo transplantation. Our data suggest biological effects of the transplanted NLB cells on tissue contractility, although robust statistical results could not be obtained due to the small sample size. Further, it is unclear, which of the NLB cell types including neural progenitors have direct restoring effects or, alternatively may act via 'bystander' mechanisms in vivo. Our findings provide further evidence that NLB transplantation can be considered as feasible tool to improve ENS function in a variety of gastrointestinal disorders.},
  language  = {en}
}
@phdthesis{Beykan2021,
  author    = {Beykan, Seval},
  title     = {Implementation and Optimization of Dosimetry for Theranostics in Radiopeptide Therapies},
  doi       = {10.25972/OPUS-19955},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199553},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Peptide receptor radionuclide therapy (PRRT) is a molecular targeted radiation therapy involving the systemic administration of radiolabeled somatostatin receptor binding peptides designed to target with high affinity and specificity receptors overexpressed on tumors. Peptides are applied which either target as agonist (with internalization) or antagonist (little to no internalization). Recently, two novel antagonistic agents have been developed for clinical use: OPS202 and OPS201. 68Ga-labelled OPS202 is used for diagnostic purposes with positron emission tomography and 177Lu-labelled OPS201 is used for the therapy in patients with neuroendocrine tumors (NETs). Both agents are presently under clinical evaluation. Despite the very low internalization rate, the use of somatostatin receptor antagonists which target more binding sites on receptors are expected to result in higher specificity, more favorable pharmacokinetics and higher tumor retention and better visualization than the agonists. The main goal of this thesis was analyzing the biodistribution, biokinetics and internal dosimetry of the recently developed somatostatin receptor antagonists (OPS201 and OPS202) for therapeutic and diagnostic purposes in different species (mice, pigs and patients). In addition, an analysis of the influence of image quantification and the integration of time activity curves on kidney dosimetry in a pig model was carried out. Furthermore, extrapolation methods, which are used for predicting organ absorbed doses for humans based on preclinical animal models, were systematically compared for blood, liver, and kidneys of OPS201 injected species. Based on the OPS202 injected patients' investigations, 68Ga-OPS202 shows promising biodistribution and imaging properties with tumor contrast which is optimal one hour after injection of the radiotracer. OPS202 is well tolerated and delivers absorbed doses to organs that are lower than those by 18F-FDG and similar to other 68Ga-labeled somatostatin receptor ligands. As a result of 68Ga OPS202 injection, the highest absorbed doses were observed in the urinary bladder (0.10 mGy/MBq) and kidneys (0.84 mGy/MBq). The calculated mean effective dose coefficient of 68Ga-OPS202 injected patients was 0.024 mSv/MBq (3.6 mSv for 150 MBq 68Ga-OPS202 injection) which is similar to other 68Ga-labeled compounds. Based on the OPS201 biokinetics and dosimetry investigations, after the injection of 177Lu-OPS201, a fast blood clearance of the compound is observed in the first phase (half-life: 1.83 h) for each species. 10 min after injection, less than 5\% of the injected activity per milliliter of blood circulates in pigs and humans. The analysis of the mice, pig and preliminary patient data provides evidence that, patients enrolled in a phase 1 177Lu-OPS201 trial would not be at risk of overexposure. Based on our results, for 177Lu labelled studies, late time points after 72 h have a great impact on absorbed dose calculations. That is why follow-up times especially at late time points (more than 72 h) are required for the time-integrated activity coefficient (TIAC) calculations in order to represent the area under the curve appropriately and to analyze both biokinetics and dosimetry accurately. In addition, to find the most adequate extrapolation methods that minimize the interspecies differences of dosimetry data, several extrapolation methods from animal to human have been tested. For OPS201 time scaling or combination of relative mass and time scaling results in most similar TIAC values, if the organ mass ratios between the species are high. In time scaling, the scan/sampling time is scaled by using the ratio of the whole body masses of the respective species. In relative mass scaling, the TIACs are scaled based on the ratio of the whole body and organ mass of respective species. Other methods tested showed higher deviations. For the study on the influence of image quantification and the choice of the optimal scanning time points, a study in a pig model, which was performed in collaboration with Aalborg University and Octreopharm Sciences GmbH, was reanalyzed. As kidneys are organs-at-risk in PRRT with 177Lu labelled peptides, several quantification methods, based on 2D and 3D quantitative imaging were chosen. For this purpose, a 3D printed pig kidney phantom was prepared and measured with/without background activities representing the activities in the pig SPECT/CT scans. The phantom dosimetry data based on multiple SPECT/CT images and based on multiple planar images in combination with one SPECT/CT scan (MP1S Imaging) were compared to the pig dosimetry. The calculated TIACs of the phantom with background based on multiple SPECT/CT and MP1S imaging were quite similar to the multiple SPECT/CT based pig TIAC. In addition, in order to investigate the effect of late time points on dosimetry and absorbed dose values in 177Lu therapies, the difference, associated with eliminating the late two scan time points, on the TIACs was analyzed. When the TIACs (including all time points) of the pig based on multiple SPECT/CT and MP1S imaging were investigated, the use of MP1S imaging results in considerably lower TIAC values to the kidney (by a factor of 1.4). With eliminating late time points from the created time activity curve, the factor increases up to 2.4 times with a corresponding increase in TIAC uncertainties. As a consequence, further evaluation of 68Ga-OPS202 for PET/CT imaging and 177Lu-OPS201 for the treatments of NET patients is necessary. In particular, a head-to-head comparison of agonists and OPS peptides with respect to biokinetics, biodistribution and dosimetry would be helpful. In addition, the influence of the late scan time points on dosimetry needs further attention in particular for kidney dosimetry},
  language  = {en}
}
@article{SterzingEngenhartCabillicFlentjeetal.2011,
  author    = {Sterzing, Florian and Engenhart-Cabillic, Rita and Flentje, Michael and Debus, J{\"u}rgen},
  title     = {Image-Guided Radiotherapy : A New Dimension in Radiation Oncology},
  series = {Deutsches {\"A}rzteblatt International},
  volume    = {108},
  journal   = {Deutsches {\"A}rzteblatt International},
  number    = {16},
  doi       = {10.3238/arztebl.2011.0274},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140771},
  pages     = {274-280},
  year      = {2011},
  abstract  = {Background: The vital importance of imaging techniques in radiation oncology now extends beyond diagnostic evaluation and treatment planning. Recent technical advances have enabled the integration of various imaging modalities into the everyday practice of radiotherapy directly at the linear accelerator, improving the management of inter-and intrafractional variations. Methods: We present the topic of image-guided radiotherapy (IGRT) on the basis of a selective review of the literature. Results: IGRT can be performed with the aid of ultrasound, 2D X-ray devices, and computed tomography. It enables instant correction for positioning deviations and thereby improves the precision of daily radiotherapy fractions. It also enables immediate adjustment for changes in the position and filling status of the internal organs. Anatomical changes that take place over the course of radiotherapy, such as weight loss, tumor shrinkage, and the opening of atelectases, can be detected as they occur and accounted for in dosimetric calculations. There have not yet been any randomized controlled trials showing that IGRT causes fewer adverse effects or improves tumor control compared to conventional radiotherapy. Conclusion: IGRT is more precise and thus potentially safer than conventional radiotherapy. It also enables the application of special radiotherapeutic techniques with narrow safety margins in the vicinity of radiosensitive organs. Proper patient selection for IGRT must take account of the goals of treatment and the planning characteristics, as well as the available technical and human resources. IGRT should be used for steep dose gradients near organs at risk, for highly conformal dose distributions in the gastrointestinal tract where adjustment for filling variations is needed, for high-precision dose escalation to avoid geographic miss, and for patients who cannot lie perfectly still because of pain or claustrophobia.},
  language  = {en}
}
@article{SchummerSchilling2022,
  author    = {Schummer, Patrick and Schilling, Bastian},
  title     = {How representative are data from global trials on programmed death-1 blockade in melanoma?},
  series = {The British Journal of Dermatology},
  volume    = {187},
  journal   = {The British Journal of Dermatology},
  number    = {3},
  doi       = {10.1111/bjd.21621},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318406},
  pages     = {283 -- 284},
  year      = {2022},
  language  = {en}
}
@article{AndersenBogstedDybkaretal.2015,
  author    = {Andersen, Jens Peter and B{\o}gsted, Martin and Dybk{\ae}r, Karen and Mellqvist, Ulf-Henrik and Morgan, Gareth J. and Goldschmidt, Hartmut and Dimopoulos, Meletios A. and Einsele, Hermann and San Miguel, Jes{\´u}s and Palumbo, Antonio and Sonneveld, Pieter and Johnsen, Hans Erik},
  title     = {Global myeloma research clusters, output, and citations: a bibliometric mapping and clustering analysis},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0116966},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144214},
  pages     = {e0116966},
  year      = {2015},
  abstract  = {Background International collaborative research is a mechanism for improving the development of disease-specific therapies and for improving health at the population level. However, limited data are available to assess the trends in research output related to orphan diseases. Methods and Findings We used bibliometric mapping and clustering methods to illustrate the level of fragmentation in myeloma research and the development of collaborative efforts. Publication data from Thomson Reuters Web of Science were retrieved for 2005-2009 and followed until 2013. We created a database of multiple myeloma publications, and we analysed impact and co-authorship density to identify scientific collaborations, developments, and international key players over time. The global annual publication volume for studies on multiple myeloma increased from 1,144 in 2005 to 1,628 in 2009, which represents a 43\% increase. This increase is high compared to the 24\% and 14\% increases observed for lymphoma and leukaemia. The major proportion (> 90\% of publications) was from the US and EU over the study period. The output and impact in terms of citations, identified several successful groups with a large number of intra-cluster collaborations in the US and EU. The US-based myeloma clusters clearly stand out as the most productive and highly cited, and the European Myeloma Network members exhibited a doubling of collaborative publications from 2005 to 2009, still increasing up to 2013. Conclusion and Perspective Multiple myeloma research output has increased substantially in the past decade. The fragmented European myeloma research activities based on national or regional groups are progressing, but they require a broad range of targeted research investments to improve multiple myeloma health care.},
  language  = {en}
}
@article{UnnewehrStich2015,
  author    = {Unnewehr, Markus and Stich, August},
  title     = {Fighting Hepatitis B in North Korea: Feasibility of a Bi-modal Prevention Strategy},
  series = {Journal of Korean Medical Science},
  volume    = {30},
  journal   = {Journal of Korean Medical Science},
  doi       = {10.3346/jkms.2015.30.11.1584},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138773},
  pages     = {1584-1588},
  year      = {2015},
  abstract  = {In North Korea, the prevalence of hepatitis B is high due to natural factors, gaps in vaccination, and the lack of antiviral treatment. Aid projects are urgently needed, however impeded by North Korea's political and economical situation and isolation. The feasibility of a joint North Korean and German humanitarian hepatitis B prevention program was assessed. Part 1: Hepatitis B vaccination catch-up campaign. Part 2: Implementation of endoscopic ligation of esophageal varices (EVL) by trainings in Germany and North Korea. By vaccinating 7 million children between 2010 and 2012, the hepatitis B vaccination gap was closed. Coverage of 99.23\% was reached. A total of 11 hepatitis B-induced liver cirrhosis patients (mean age 41.1 yr) with severe esophageal varices and previous bleedings were successfully treated by EVL without major complications. A clinical standard operating procedure, a feedback system and a follow-up plan were developed. The bi-modal preventive strategy was implemented successfully. Parts of the project can serve as an example for other low-income countries, however its general transferability is limited due to the special circumstances in North Korea.},
  language  = {en}
}
@phdthesis{Stanescu2005,
  author    = {Stanescu, Angela},
  title     = {Fieber und Neutropenie bei krebskranken Kindern - prognostische Faktoren und Therapie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-12150},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Onkologische Patienten sind w{\"a}hrend der Phase der Chemotherapie-bedingten Knochenmarkdepression besonders durch Infektionen bedroht. Da bisher keine Parameter bekannt sind, die eine schwerwiegende bakterielle Infektion zu Beginn einer Fieberepisode von anderen Fieberursachen sicher differenziert, werden diese Patienten bei Fieber und Neutropenie trotz der damit verbundenen Nachteile und Risiken, wie z.B. m{\"o}gliche Resistenzbildung, Toxizit{\"a}t der Antibiotika, Risiko nosokomialer Infektionen, psychische Belastung der kleinen Patienten und deren Eltern, sofort station{\"a}r aufgenommen und intraven{\"o}s mit Antibiotika behandelt. In der vorliegenden Studie wurde der diagnostische Wert der Interleukine 6 und -8 f{\"u}r die Fr{\"u}herkennung schwerer Infektionen bei p{\"a}diatrischen Patienten mit Fieber und Chemotherapie-bedingter Neutropenie untersucht und mit dem diagnostischen Wert des CrP verglichen. In einem Beobachtungszeitraum von 15 Monaten wurden in 128 Fieberepisoden bei 55 Patienten mit einem breiten Spektrum onkologischer Grunderkrankungen die Konzentrationen der Parameter an den ersten Fiebertagen bestimmt. Neben 95 FUO-Episoden wurden sechs bakterielle Infektionen mit gram-negativem Erreger, 19 bakterielle Infektionen mit gram-positivem Erreger, drei Pilzinfektionen und f{\"u}nf klinisch dokumentierte Infektionen behandelt. Es zeigten sich signifikant h{\"o}here IL-6 und IL-8 Konzentrationen am ersten Fiebertag bei Infektionen mit gram-negativen Bakterien, S.aureus und Pilzen, also bei potentiell schwerer verlaufenden Infektionen als bei FUO, S.epidermidis- und klinisch dokumentierten Infektionen. Schwere Infektionen konnten mit einer deutlich h{\"o}heren Sensitivit{\"a}t und Spezifit{\"a}t von anderen Fieberursachen durch die Interleukine als durch das CrP unterschieden werden. Die Interleukine-6 und -8 k{\"o}nnten im Gegensatz zum CrP eine wertvolle Hilfe in der Fr{\"u}hdiagnostik von schwerwiegenden Infektionen bei p{\"a}diatrischen Patienten mit chemotherapiebedingter Neutropenie und Fieber sein. Die in dieser Arbeit dargestellten Ergebnisse m{\"u}ssen jedoch vor einem routinem{\"a}ßigen Einsatz im Klinikalltag in großen, prospektiven Studien validiert werden. Ein weiteres Ziel dieser Studie war, den Therapieerfolg einer initialen Monotherapie mit Imipenem/Cilastat zur Behandlung von Kindern mit Fieber und Chemotherapie-bedingter Neutropenie zu untersuchen und mit dem Therapieerfolg einer initialen Therapie mit einer Ceftazidim/Teicoplanin Kombination zu vergleichen. In insgesamt 106 auswertbaren Fieberepisoden wurde 54 mal initial mit der Monotherapie und 52 mal initial mit der Kombinationstherapie behandelt. Die antibiotische Therapie wurde nach einer Mindestdauer von 72 Stunden beendet, wenn der Patient 24 Stunden fieberfrei war und die Kriterien f{\"u}r FUO erf{\"u}llt waren, d.h., kein Erreger nachgewiesen werden konnte und keine weiteren klinischen Zeichen einer Infektion bestanden. Keiner der Patienten verstarb infolge einer Infektion. Rund die H{\"a}lfte der Patienten entfieberten in beiden Therapiegruppen innerhalb von drei Tagen unter der Initialtherapie. Beide Therapiegruppen unterschieden sich nicht signifikant hinsichtlich der Therapiedauer, der Fieberdauer und hinsichtlich der Rezidivh{\"a}ufigkeit und waren damit gleich effektiv. Lediglich bei den Infektionen mit gram-positiven Eregern zeigte sich erwartungsgem{\"a}ß, dass die initiale Kombinationstherapie aufgrund des Teicoplaninanteils zu einer rascheren Entfieberung f{\"u}hrte. Alle Patienten, die initial mit der Imipenemmonotherapie behandelt wurden, konnten nach Eintreffen des Antibiogramms erfolgreich behandelt werden. Glykopeptide sind Reserveantibiotika, die m{\"o}glichst gezielt und sparsam eingesetzt werden sollten, um einer Resistenzbildung vorzubeugen. In dieser Studie konnte gezeigt werden, dass auch der verz{\"o}gerte Einsatz von Teicoplanin in der Folgetherapie bzw. in Kenntnis des Antibiogramms den Therapieerfolg nicht signifikant vermindert und dadurch keine bedrohliche Situation f{\"u}r einen Patienten entstand. Vorteile einer Monotherapie sind außerdem eine potentiell geringere Toxiziti{\"a}t, und ein potentiell geringerer Kosten- und Personalaufwand. Wir ziehen aus den genannten Gr{\"u}nden eine initiale Monotherapie mit Imipenem einer initialen Therapie mit einer Ceftazidim/Teicoplanin Kombination vor. Nach fr{\"u}hzeitiger Beendigung der antibiotischen Therapie bei Patienten mit FUO unabh{\"a}ngig von der Granulozytenzahl im Blutbild kam es zu keiner H{\"a}ufung von Rezidiven. Mit dieser Praxis k{\"o}nnte sich nicht nur das Risiko einer Resistenzbildung senken lassen. Ein verk{\"u}rzter station{\"a}rer Aufenthalt verbessert die Lebensqualit{\"a}t der Patienten, nicht zuletzt bedeutet dies auch einen geringeren Kosten- und Personalaufwand.},
  language  = {de}
}
@article{SchulmeyerFaschingHaeberleetal.2023,
  author    = {Schulmeyer, Carla E. and Fasching, Peter A. and H{\"a}berle, Lothar and Meyer, Julia and Schneider, Michael and Wachter, David and Ruebner, Matthias and P{\"o}schke, Patrik and Beckmann, Matthias W. and Hartmann, Arndt and Erber, Ramona and Gass, Paul},
  title     = {Expression of the immunohistochemical markers CK5, CD117, and EGFR in molecular subtypes of breast cancer correlated with prognosis},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {3},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13030372},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304987},
  year      = {2023},
  abstract  = {Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort-case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS.},
  language  = {en}
}
@article{RommelMildeEberleetal.2020,
  author    = {Rommel, Marcel G. E. and Milde, Christian and Eberle, Regina and Schulze, Harald and Modlich, Ute},
  title     = {Endothelial-platelet interactions in influenza-induced pneumonia: A potential therapeutic target},
  series = {Anatomia, Histologia, Embryologia},
  volume    = {49},
  journal   = {Anatomia, Histologia, Embryologia},
  number    = {5},
  doi       = {10.1111/ahe.12521},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213610},
  pages     = {606 -- 619},
  year      = {2020},
  abstract  = {Every year, influenza viruses spread around the world, infecting the respiratory systems of countless humans and animals, causing illness and even death. Severe influenza infection is associated with pulmonary epithelial damage and endothelial dysfunction leading to acute lung injury (ALI). There is evidence that an aggressive cytokine storm and cell damage in lung capillaries as well as endothelial/platelet interactions contribute to vascular leakage, pro-thrombotic milieu and infiltration of immune effector cells. To date, treatments for ALI caused by influenza are limited to antiviral drugs, active ventilation or further symptomatic treatments. In this review, we summarize the mechanisms of influenza-mediated pathogenesis, permissive animal models and histopathological changes of lung tissue in both mice and men and compare it with histological and electron microscopic data from our own group. We highlight the molecular and cellular interactions between pulmonary endothelium and platelets in homeostasis and influenza-induced pathogenesis. Finally, we discuss novel therapeutic targets on platelets/endothelial interaction to reduce or resolve ALI.},
  language  = {en}
}
@phdthesis{Bergfeld2001,
  author    = {Bergfeld, Simone},
  title     = {Ellenbogenfrakturen im Kindesalter mit Ausnahme der suprakondyl{\"a}ren Humerusfraktur},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1181052},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2001},
  abstract  = {Ziel: Darstellung der verschiedenen Ellenbogenfrakturen im Kindesalter mit Ausnahme der suprakondyl{\"a}ren Humerusfraktur bez{\"u}glich ihrer H{\"a}ufigkeit, Therapiem{\"o}glichkeiten und typischen Komplikationen. Weiterhin Beurteilung der verschiedenen Therapiestrategien der einzelnen Frakturtypen unter Ber{\"u}cksichtigung der Schwere des Prim{\"a}rtraumas und der vorhandenen Begleitver-letzungen. Material und Methoden: Erfassung aller 73 kindlichen Patienten, die von 1984-1993 an der Chirurgischen Universit{\"a}tsklinik mit Ellenbogenfrakturen ausgenommen der suprakondyl{\"a}ren Humerusfraktur behandelt worden sind anhand der Krankenunterlagen und Bewertung der Ergebnisse der Nachuntersuchung von 48 Patienten 3-14 Jahre nach dem Unfall anhand der Klassifikation nach MORGER, welche auf dem Ausmaß von Bewegungseinschr{\"a}nkungen nach der Neutral-Null-Methode und Achsabweichungen der Ellenbogenachse in Grad basiert. Ergebnis: Insgesamt fand sich 21 mal ein ideales, 22 mal ein gutes, 1 mal ein befriedigendes und 4 mal ein schlechtes Ergebnis bei der Nachuntersuchung. Die h{\"a}ufigste Fraktur war die des Condylus radialis, gefolgt von der Epicondylus ulnaris Fraktur und der Fraktur des proximalen Radiusendes. Die {\"u}brigen Frakturen kamen nur selten vor. Bei den Condylus radialis Frakturen stellten sich Kompressionsosteosythesetechniken im Hinblick auf zu vermeidende Wachstumsst{\"o}rungen als vorteilhaft gegen{\"u}ber reinen Spickdrahtosteosynthesen dar. Bei den {\"u}brigen Frakturen konnte kein Osteosyntheseverfahren als eindeutig geeigneter beurteilt werden. Wichtig erscheint, dass bei Condylus radialis Frakturen und Epicondylus ulnaris Frakturen beim Vorliegen einer Fragmentdislokation und bei Frakturen des proximalen Radiusendes ab einem bestimmten Dislokationsgrad operative Therapieverfahren zur Anwendung kommen sollten. Insgesamt korreliert das Ergebnis der Nachuntersuchungen in erster Linie in entscheidendem Ausmaß mit der Schwere der Prim{\"a}rverletzung. Die Folgen starker Traumatisierungen des Kapsel-Band-Apparates stellten sich hierbei als besonders ung{\"u}nstig und therapeutisch schwierig zu beeinflussend dar.},
  language  = {de}
}
@phdthesis{Weiss2021,
  author    = {Weiß, Claire Rachel},
  title     = {Einfluss adjuvanter Therapien des initial hormonrezeptorpositiven Mammakarzinoms auf die Entwicklung einer Rezeptorkonversion im Rezidiv},
  doi       = {10.25972/OPUS-22181},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221814},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {In der vorliegenden Arbeit erfolgte eine retrospektive Auswertung der Daten von 2078 Patienten mit Erstdiagnose eines prim{\"a}r hormonrezeptorpositivem Mammakarzinoms, bez{\"u}glich der Entwicklung einer Rezeptorkonversion im Rezidiv. 196 Frauen entwickelten ein Rezidiv, wovon 29,1\% eine Rezeptorver{\"a}nderung im {\"O}strogen-, Progesteron-, oder HER2-neu-Rezeptor zeigten. Ein niedriger Tumordifferenzierungsgrad und eine axill{\"a}re Lymphknotenbeteiligung zeigten ein erh{\"o}htes Risiko f{\"u}r das Auftreten einer Rezeptorkonversion. Eine pr{\"a}menopausale Tamoxifentherapie oder die Applikation einer Chemotherapie war mit einem geringerem Risiko f{\"u}r die Entwicklung eines {\"o}strogenrezeptornegativen Rezidivs assoziiert. Der Verlust der Rezeptorpositivit{\"a}t zeigte einen Trend zu einem geringeren Gesamt{\"u}berleben.},
  subject      = {Adjuvante Therapie},
  language  = {de}
}
@phdthesis{Caspari2024,
  author    = {Caspari, Almut},
  title     = {Effektivit{\"a}t von APD421 (Amisulprid zur i.v.-Injektion) zur PONV-Therapie nach fehlgeschlagener PONV-Prophylaxe. Eine prospektive, randomisierte, Placebo-kontrollierte Doppelblindstudie.},
  doi       = {10.25972/OPUS-34733},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-347331},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Postoperative {\"U}belkeit und postoperatives Erbrechen (PONV) sind eine der h{\"a}ufigsten und f{\"u}r Patient*innen unangenehmsten Nebenwirkungen einer Allgemeinan{\"a}sthesie. Trotz jahrzehntelanger Forschung und der Vielfalt an mittlerweile bekannten Maßnahmen und Substanzen zur PONV-Prophylaxe und -Therapie gibt es noch keine Strategie, die eine sichere Vermeidung oder stets wirksame Therapie von PONV garantieren kann. In vorangegangenen Studien zeigte Amisulprid als Dopaminantagonist an den Rezeptortypen D2 und D3 vielversprechende Ergebnisse zur PONV-Prophylaxe und -Therapie. Die dieser Arbeit zugrunde liegende prospektive, randomisierte, Placebo-kontrollierte Doppelblindstudie untersuchte die Wirksamkeit einer Einzeldosis APD421 5 mg bzw. 10 mg zur Therapie von manifestem PONV nach fehlgeschlagener PONV-Prophylaxe. „Complete Response" (CR) wurde definiert als das Ausbleiben jeglicher weiterer emetischer Episoden im Zeitraum von 30 Minuten bis 24 Stunden nach Applikation des Studienmedikaments sowie keine Gabe von antiemetischer Rescue-Medikation im gesamten Zeitraum bis 24 Stunden nach Applikation des Studienmedikaments. Die CR-Raten lagen bei 41,7\% f{\"u}r APD421 10 mg, 33,8\% f{\"u}r APD421 5 mg und 28,5\% f{\"u}r Placebo, wobei die Studienarme jeweils 230, 237 bzw. 235 Patient*innen umfassten. Eine Dosis APD421 10 mg zeigte somit statistisch signifikante {\"U}berlegenheit in der PONV-Therapie gegen{\"u}ber Placebo. Auch hinsichtlich sekund{\"a}rer Studienendpunkte wie Auftreten bzw. St{\"a}rke von {\"U}belkeit, W{\"u}rgen oder Erbrechen und Bedarf an Rescue-Medikation war APD421 10 mg gegen{\"u}ber Placebo {\"u}berlegen. Eine Dosis von 5 mg APD421 zeigte f{\"u}r die meisten Endpunkte hingegen keine statistisch signifikante {\"U}berlegenheit gegen{\"u}ber Placebo. Limitationen der Studie liegen im Ausschluss von Patientengruppen wie beispielsweise Kindern oder bestimmten Vorerkrankungen und dem mit {\"u}ber 90\% sehr hohen Anteil weiblicher Patient*innen. Es bleiben weitere Studien abzuwarten, die APD421 einem direkten Vergleich mit bislang etablierten Substanzen zur PONV-Therapie unterziehen, um den k{\"u}nftigen Stellenwert der Substanz im klinischen Alltag einsch{\"a}tzen zu k{\"o}nnen.},
  subject      = {Amisulprid},
  language  = {de}
}
@article{FeldheimKesslerFeldheimetal.2022,
  author    = {Feldheim, Jonas and Kessler, Almuth F. and Feldheim, Julia J. and Schulz, Ellina and Wend, David and Lazaridis, Lazaros and Kleinschnitz, Christoph and Glas, Martin and Ernestus, Ralf-Ingo and Brandner, Sebastian and Monoranu, Camelia M. and L{\"o}hr, Mario and Hagemann, Carsten},
  title     = {Effects of long-term temozolomide treatment on glioblastoma and astrocytoma WHO grade 4 stem-like cells},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {9},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23095238},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284417},
  year      = {2022},
  abstract  = {Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O\(^6\)-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.},
  language  = {en}
}
@article{WeissenbergerWeissenbergerWagenbrenneretal.2020,
  author    = {Weissenberger, Manuel and Weissenberger, Manuela H. and Wagenbrenner, Mike and Heinz, Tizian and Reboredo, Jenny and Holzapfel, Boris M. and Rudert, Maximilian and Groll, J{\"u}rgen and Evans, Christopher H. and Steinert, Andre F.},
  title     = {Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer},
  series = {PLoS One},
  volume    = {15},
  journal   = {PLoS One},
  number    = {8},
  doi       = {10.1371/journal.pone.0237479},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230494},
  year      = {2020},
  abstract  = {Objective As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. Design Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX)9,transforming growth factor beta (TGFB) 1or bone morphogenetic protein (BMP) 2cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. Results Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenesSOX9,TGFB1andBMP2as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups (BMP2>TGFB1>SOX9). Conclusions Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factorsSOX9,TGFB1andBMP2. This technology may be harnessed for regeneration of specific zones of native cartilage upon damage.},
  language  = {en}
}
@phdthesis{Lorenzen2004,
  author    = {Lorenzen, Axel},
  title     = {Die Arthroskopie bei Erkrankungen des Handgelenks},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-9903},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Von Oktober 1992 bis Januar 1998 wurden in der Handchirurgie der Chirurgischen Universit{\"a}tsklinik W{\"u}rzburg 137 Patienten mit akuten und chronischen Handgelenksschmerzen arthroskopiert. Von diesen konnten 55 nachuntersucht werden, davon waren 45 M{\"a}nner und 10 Frauen. Der Altersdurchschnitt lag bei 40 Jahren. Entsprechend dem arthroskopischen Befund wurden die Patienten retrospektiv in sechs Gruppen eingeteilt. Das Ergebnis wurde mit dem Mayo Modified Wrist Score und mit dem Krimmer-Score evaluiert. Bei der Gruppe mit Ulnar Impaction Syndrome infolge prim{\"a}rer oder sekund{\"a}rer Ulnaplusvariante (n=10) konnten mit Wafer-Resections und Ulnaverk{\"u}rzungen sehr gute Ergebnisse erreicht werden. Durch diese Behandlungsmethoden bleibt der TFCC in Form und Funktion erhalten und wird optimal entlastet. Die Handgelenksbeweglichkeit betrug postoperativ 76 \% im Vergleich zur Gegenseite, die Kraft 63 \%. Bei 60 \% der Patienten kam es zu einer Schmerzlinderung. Bei skapholun{\"a}ren Dissoziationen ist die Behandlung vom Grad der Verletzung abh{\"a}ngig. Bei den Patienten mit erstgradiger skapholun{\"a}rer Dissoziation (n=12) konnten gute Ergebnisse mit konservativer Behandlung, D{\´e}bridement und Denervationen erzielt werden. Hier betrug die Handgelenksbeweglichkeit postoperativ 91 \% im Vergleich zur Gegenseite, die Kraft 73 \%. 75 \% der Patienten gaben eine Schmerzlinderung an. Die Patienten mit zweitgradiger skapholun{\"a}rer Dissoziation (n=5) wurden entweder konservativ oder operativ mit Bandnaht, D{\´e}bridement oder Denervation behandelt. Postoperativ betrug die Handgelenksbeweglichkeit 83 \% im Vergleich zur Gegenseite, die Kraft 63 \%. Ein Patient hatte bei der Nachuntersuchung keine Schmerzen mehr, einer gab eine deutliche Besserung an, drei gaben eine Zunahme der Schmerzen an. Drei beurteilten das Ergebnis als sehr gut und 2 als mangelhaft. Bei zweitgradigen skapholun{\"a}ren Dissoziationen waren konservatives Vorgehen und D{\´e}bridement auf lange Sicht nicht ausreichend, die Entwicklung zum schmerzhaften SLAC-Wrist zu verhindern. Die Patienten mit drittgradiger skapholun{\"a}rer Dissoziation (n=4) erreichten nach einer mediokarpalen Teilarthrodese eine Handgelenksbeweglichkeit von 61 \% und eine Kraft von 35 \% im Vergleich zur Gegenseite. Drei der vier Patienten gaben eine Schmerzlinderung an. Bei den Patienten mit erst- bis zweitgradiger Arthrose des Radiokarpalgelenks ohne skapholun{\"a}re Dissoziation und Ulnar Impaction Syndrome (n=14) konnte sowohl mit konservativer Behandlung als auch mit einem arthroskopischen D{\´e}bridement der B{\"a}nder und der Knorpelfl{\"a}chen eine zuverl{\"a}ssige Beschwerdebesserung erreicht werden. Postoperativ betrug die Handgelenksbeweglichkeit durchschnittlich 89 \% und die Kraft 85 \% im Vergleich zur Gegenseite. 86 \% der Patienten gaben eine Schmerzlinderung an. In der Gruppe mit dritt- bis viertgradiger Arthrose im Radiokarpalgelenk ohne skapholun{\"a}re Dissoziation und Ulnar Impaction Syndrome (n=10) wurden zur Behandlung das D{\´e}bridement, die Denervation und die Arthrodese eingesetzt. Dabei konnte nur mit der Denervation eine Schmerzlinderung erreicht werden (einer schmerzfrei, 4 deutlich verringert, einer unver{\"a}ndert). Nach D{\´e}bridement und Arthrodese blieb der Schmerz unver{\"a}ndert oder verschlechterte sich. Nach der Denervation waren die Handgelenksbeweglichkeit mit 87 \% der Gegenseite und die Kraft mit 75 \% etwa doppelt so groß wie nach D{\´e}bridement oder Arthrodese. Mit Hilfe der Handgelenksarthroskopie konnte in allen F{\"a}llen die richtige Diagnose gestellt werden. Nach den Kriterien von Jackson und Abe (modifiziert von Morrey) konnte mit den Informationen aus der Gelenkspiegelung in 65 \% der F{\"a}lle die pr{\"a}operative Diagnose korrigiert werden beziehungsweise erstmals eine Erkl{\"a}rung f{\"u}r die Beschwerden gefunden werden. In 35 \% wurde die pr{\"a}operative Diagnose best{\"a}tigt.},
  language  = {de}
}
@phdthesis{Thorwarth2006,
  author    = {Thorwarth, Christian},
  title     = {Diagnostische und therapeutische chirurgische Konzepte bei intestinaler Isch{\"a}mie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-18191},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Im Rahmen der vorliegenden Arbeit erfolgte eine retrospektive Analyse von 86 Patienten der Chirurgischen Universit{\"a}tsklinik W{\"u}rzburg die von 02/1995 bis 07/2002 aufgrund mesenterialer Isch{\"a}mien therapiert werden mussten. Ziel der Untersuchung war eine Bewertung aktueller diagnostischer und therapeutischer M{\"o}glichkeiten und deren Einfluss auf die Erfolgsprognose der Erkrankung. Das klinische Erscheinungsbild der akuten Verschlussformen war gerade in der entscheidenden Fr{\"u}hphase sehr uncharakteristisch. Daher kommt der sorgf{\"a}ltigen Anamneseerhebung eine große Bedeutung zu. Bei der chronischen mesenterialen Isch{\"a}mie kommt es zu postprandialen Schmerzen und Gewichtsverlust, meist als akute Verschlimmerung eines Dauerschmerzes etwa 10 - 30 Minuten nach einer Mahlzeit mit Regredienz innerhalb der n{\"a}chsten Stunden. Als diagnostische Verfahren kamen Sonografie, Nativaufnahme, Duplex-, Farbduplexsonografie und Computertomografie zum Einsatz. Alleine mit Hilfe der intraarteriellen Subtraktionsangiografie gelang ein zuverl{\"a}ssiger Nachweis akuter oder chronischer viszeraler Isch{\"a}mien. Ist die angiografische Abkl{\"a}rung aufgrund mangelnder apparativer Ausstattung nicht m{\"o}glich, muss z{\"u}gig eine diagnostische Laparoskopie durchgef{\"u}hrt werden. Eine typische Konstellation von Laborparametern konnte zu diesem Zeitpunkt nicht erhoben werden. Lediglich dem Serumlaktat kam eine Bedeutung zu, jedoch ließ die H{\"o}he keine R{\"u}ckschl{\"u}sse auf die Ausdehnung der isch{\"a}mischen Bezirke zu. Operative Therapieverfahren haben die m{\"o}glichst schnelle Strombahnwiederherstellung und Revaskularisiation der infarktbedrohten Darmabschnitte zum Ziel. Die alleinige Darmresektion ist angezeigt, wenn eine Gef{\"a}ßrekonstruktion technisch nicht m{\"o}glich erscheint. Arterielle Rekonstruktionsverfahren wie Embolektomie oder Methoden mit Gef{\"a}ßersatz- bzw. Transplantatmaterial sind indiziert, wenn die M{\"o}glichkeit einer Restitutio nach Perfusionswiederherstellung besteht. Eine prophylaktische Rekonstruktion bei asymptomatischen Viszeralarterienverschluss scheint bei der chronischen Verlaufsform nicht sinnvoll. Die Indikation f{\"u}r eine second - look Operation sollte großz{\"u}gig gestellt werden! Bei kurzstreckiger Verschlussmorphologie erscheinen Stenosen der Viszeralarterien auch f{\"u}r perkutane transluminale Angioplastie geeignet. Bei der nicht okklusiven Form der Mesenterialisch{\"a}mie haben kardiologisch - intensivmedizinische Maßnahmen als alleinige Therapie Vorrang. Der wichtigste prognostische Faktor f{\"u}r die erfolgreiche Behandlung und damit auch f{\"u}r die Gesamtprognose der akuten Verlaufsform ist die fr{\"u}hzeitige Diagnosestellung und Behandlung.},
  language  = {de}
}
@article{StrobelSickenbergerSchoenetal.2022,
  author    = {Strobel, Katharina and Sickenberger, Christina and Schoen, Christoph and Kneitz, Hermann and Kolb-M{\"a}urer, Annette and Goebeler, Matthias},
  title     = {Diagnosis and therapy of Mycobacterium marinum: a single-center 21-year retrospective analysis},
  series = {Journal der Deutschen Dermatologischen Gesellschaft},
  volume    = {20},
  journal   = {Journal der Deutschen Dermatologischen Gesellschaft},
  number    = {9},
  doi       = {10.1111/ddg.14847},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318428},
  pages     = {1211 -- 1218},
  year      = {2022},
  abstract  = {Background and Objectives In Europe, infections with Mycobacterium (M.) marinum are rare. We conducted a retrospective single-center study to assess the clinical spectrum of M. marinum infection and its diagnosis, treatment and outcome under real-world conditions. Patients and Methods Eighteen patients presenting with M. marinum infections between 1998 and 2018 were identified in the data warehouse of the University Hospital W{\"u}rzburg and considered for detailed analysis. Results Twelve patients reported aquatic exposure. In 16/18 cases the upper extremities were affected. No invasive infections were detected. Mean time to diagnosis was 15 weeks. Histology revealed granulomatous inflammation in 14 patients while mycobacterial cultures were positive for M. marinum in 16 cases. Most patients received antibiotic monotherapy (14/18) while combination therapy was administered in four cases. Treatment (with a median duration of 10 weeks) was successful in 13 patients. Five patients were lost to follow-up. Conclusions Our retrospective analysis of M. marinum infections at a German tertiary referral center revealed a considerable diagnostic delay and the relevance of microbiological culture, PCR and histology for diagnosis. Monotherapy with clarithromycin (rather than doxycycline) appeared as a reasonable treatment option while immunosuppressed or -compromised patients and those with extended disease received combination therapy.},
  language  = {en}
}
@phdthesis{Schaefer2014,
  author    = {Schaefer, Frauke},
  title     = {Diagnosis and therapy of malaria under the conditions of a developing country - the example of Burkina Faso},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-102863},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Malaria is a challenging infection with increasing and wide-spread treatment failure risk due to resistance. With a estimated death toll of 1-3 Million per year, most cases of Malaria affect children under the age of five years in Sub-Saharan Africa. In this thesis, I analyse the current status of malaria control (focussing on diagnosis and therapy) in Burkina Faso to show how this disease burdens public health in endemic countries and to identify possible approaches to improvement. MB is discussed as a therapeutic option under these circumstances. Burkina Faso is used as a representative example for a country in Sub-Saharan Africa with high endemicity for malaria and is here portrayed, its health system characterised and discussed under socioeconomic aspects. More than half of this country's population live in absolute poverty. The burden that malaria, especially treatment cost, poses on these people cannot be under-estimated. A retrospective study of case files from the university pediatric hospital in Burkina Faso's capital, Ouagadougou, shows that the case load is huge, and especially the specific diagnosis of severe malaria is difficult to apply in the hospital's daily routine. Treatment policy as proposed by WHO is not satisfactorily implemented neither in home treatment nor in health services, as data for pretreatment clearly show. In the face of growing resistance in malaria parasites, pharmacological combination therapies are important. Artemisinins currently are the last resort of malaria therapy. As I show with homology models, even this golden bullet is not beyond resistance development. Inconsidered mass use has rendered other drugs virtually useless before. Artemisinins should thus be protected similar to reserve antibiotics against multi-resistant bacteria. There is accumulating evidence that MB is an effective drug against malaria. Here the biological effects of both MB alone and in combination therapy is explored via modeling and experimental data. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, CQ resistance based on Pfmdr1 and PfCRT transporters as well as SP resistance were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs, given their correct application. Also from the economic point of view MB shows great potential: in terms of production price, it can be compared to CQ, which could help to diminuish the costs of malaria treatment to affordable ranges for those most affected and struk by poverty. Malaria control is feasible, but suboptimal diagnosis and treatment are often hindering the achievment of this goal. In order to achieve malaria control, more effort has to be made to implement better adjusted and available primary treatment strategies for uncomplicated malaria that are highly standardised. Unfortunately, campaigns against malaria are chronically underfinanced. In order to maximize the effect of available funds, a cheap treatment option is most important, especially as pharmaceuticals represent the biggest single matter of expense in the fight against malaria.},
  subject      = {Malaria},
  language  = {en}
}
@article{DimopoulosWeiselSongetal.2015,
  author    = {Dimopoulos, Meletios A. and Weisel, Katja C. and Song, Kevin W. and Delforge, Michel and Karlin, Lionel and Goldschmidt, Hartmut and Moreau, Philippe and Banos, Anne and Oriol, Albert and Garderet, Laurent and Cavo, Michele and Ivanova, Valentina and Alegre, Adrian and Martinez-Lopez, Joaquin and Chen, Christine and Spencer, Andrew and Knop, Stefan and Bahlis, Nizar J. and Renner, Christoph and Yu, Xin and Hong, Kevin and Sternas, Lars and Jacques, Christian and Zaki, Mohamed H. and San Miguel, Jesus F.},
  title     = {Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone},
  series = {Haematologica},
  volume    = {100},
  journal   = {Haematologica},
  number    = {10},
  doi       = {10.3324/haematol.2014.117077},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140349},
  pages     = {1327 -- 1333},
  year      = {2015},
  abstract  = {Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P < 0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or highdose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2\% versus 9.7\%) and those with del(17p) (31.8\% versus 4.3\%), whereas it was similar in patients with t(4; 14) (15.9\% versus 13.3\%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del(17p) and/or t(4;14).},
  language  = {en}
}
@article{EsmaeilpourBroscheitShityakov2022,
  author    = {Esmaeilpour, Donya and Broscheit, Jens Albert and Shityakov, Sergey},
  title     = {Cyclodextrin-based polymeric materials bound to corona protein for theranostic applications},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {21},
  issn      = {1422-0067},
  doi       = {10.3390/ijms232113505},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297399},
  year      = {2022},
  abstract  = {Cyclodextrins (CDs) are cyclic oligosaccharide structures that could be used for theranostic applications in personalized medicine. These compounds have been widely utilized not only for enhancing drug solubility, stability, and bioavailability but also for controlled and targeted delivery of small molecules. These compounds can be complexed with various biomolecules, such as peptides or proteins, via host-guest interactions. CDs are amphiphilic compounds with water-hating holes and water-absorbing surfaces. Architectures of CDs allow the drawing and preparation of CD-based polymers (CDbPs) with optimal pharmacokinetic and pharmacodynamic properties. These polymers can be cloaked with protein corona consisting of adsorbed plasma or extracellular proteins to improve nanoparticle biodistribution and half-life. Besides, CDs have become famous in applications ranging from biomedicine to environmental sciences. In this review, we emphasize ongoing research in biomedical fields using CD-based centered, pendant, and terminated polymers and their interactions with protein corona for theranostic applications. Overall, a perusal of information concerning this novel approach in biomedicine will help to implement this methodology based on host-guest interaction to improve therapeutic and diagnostic strategies.},
  language  = {en}
}
@article{KolbMaeurerGoebelerMaeurer2015,
  author    = {Kolb-M{\"a}urer, Annette and Goebeler, Matthias and M{\"a}urer, Mathias},
  title     = {Cutaneous adverse events associated with interferon-\(\beta\) treatment of multiple sclerosis},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms160714951},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148451},
  pages     = {14951-14960},
  year      = {2015},
  abstract  = {Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-\(\beta\) who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.},
  language  = {en}
}
@article{RiedererterMeulen2020,
  author    = {Riederer, Peter and ter Meulen, Volker},
  title     = {Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses},
  series = {Journal of Neural Transmission},
  volume    = {127},
  journal   = {Journal of Neural Transmission},
  number    = {9},
  issn      = {0300-9564},
  doi       = {10.1007/s00702-020-02230-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314637},
  pages     = {1217-1228},
  year      = {2020},
  abstract  = {While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.},
  language  = {en}
}
@article{ProjahnSimsekyilmazSinghetal.2014,
  author    = {Projahn, Delia and Simsekyilmaz, Sakine and Singh, Smriti and Kanzler, Isabella and Kramp, Birgit K. and Langer, Marcella and Burlacu, Alexandrina and Bernhagen, J{\"u}rgen and Klee, Doris and Zernecke, Alma and Hackeng, Tilman M. and Groll, J{\"u}rgen and Weber, Christian and Liehn, Elisa A. and Koenen, Roy R.},
  title     = {Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction},
  series = {Journal of Cellular and Molecular Medicine},
  volume    = {18},
  journal   = {Journal of Cellular and Molecular Medicine},
  number    = {5},
  issn      = {1582-4934},
  doi       = {10.1111/jcmm.12225},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116597},
  pages     = {790-800},
  year      = {2014},
  abstract  = {Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.},
  language  = {en}
}
@article{PaholcsekFidlerKonyaetal.2015,
  author    = {Paholcsek, Melinda and Fidler, Gabor and Konya, Jozsef and Rejto, Laszlo and Mehes, Gabor and Bukta, Evelin and Loeffler, Juergen and Biro, Sandor},
  title     = {Combining standard clinical methods with PCR showed improved diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia},
  series = {BMC Infectious Diseases},
  volume    = {15},
  journal   = {BMC Infectious Diseases},
  number    = {251},
  doi       = {10.1186/s12879-015-0995-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151607},
  year      = {2015},
  abstract  = {Background: We assessed the diagnostic value of standard clinical methods and combined biomarker testing (galactomannan assay and polymerase chain reaction screening) in a prospective case-control study to detect invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia. Methods: In this observational study 162 biomarker analyses were performed on samples from 27 febrile neutropenic episodes. Sera were successively screened for galactomannan antigen and for Aspergillus fumigatus specific nucleic acid targets. Furthermore thoracic computed tomography scanning was performed along with bronchoscopy with lavage when clinically indicated. Patients were retrospectively stratified to define a case-group with "proven" or "probable" invasive pulmonary aspergillosis (25.93 \%) and a control-group of patients with no evidence for of invasive pulmonary aspergillosis (74.07 \%). In 44.44 \% of episodes fever ceased in response to antibiotic treatment (group II). Empirical antifungal therapy was administered for episodes with persistent or relapsing fever (group I). 48.15 \% of patients died during the study period. Postmortem histology was pursued in 53.85 \% of fatalities. Results: Concordant negative galactomannan and computed tomography supported by a polymerase chain reaction assay were shown to have the highest discriminatory power to exclude invasive pulmonary aspergillosis. Bronchoalveolar lavage was performed in 6 cases of invasive pulmonary aspergillosis and in 15 controls. Although bronchoalveolar lavage proved negative in 93 \% of controls it did not detect IPA in 86 \% of the cases. Remarkably post mortem histology convincingly supported the presence of Aspergillus hyphae in lung tissue from a single case which had consecutive positive polymerase chain reaction assay results but was misdiagnosed by both computed tomography and consistently negative galactomannan assay results. For the galactomannan enzyme-immunoassay the diagnostic odds ratio was 15.33 and for the polymerase chain reaction assay it was 28.67. According to Cohen's kappa our in-house polymerase chain reaction method showed a fair agreement with the galactomannan immunoassay. Combined analysis of the results from the Aspergillus galactomannan enzyme immunoassay together with those generated by our polymerase chain reaction assay led to no misdiagnoses in the control group. Conclusion: The data from this pilot-study demonstrate that the consideration of standard clinical methods combined with biomarker testing improves the capacity to make early and more accurate diagnostic decisions.},
  language  = {en}
}
@article{FeldheimKesslerMonoranuetal.2019,
  author    = {Feldheim, Jonas and Kessler, Almuth F. and Monoranu, Camelia M. and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten},
  title     = {Changes of O\(^6\)-Methylguanine DNA Methyltransferase (MGMT) promoter methylation in glioblastoma relapse—a meta-analysis type literature review},
  series = {Cancers},
  volume    = {11},
  journal   = {Cancers},
  number    = {12},
  issn      = {2072-6694},
  doi       = {10.3390/cancers11121837},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193040},
  year      = {2019},
  abstract  = {Methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter has emerged as strong prognostic factor in the therapy of glioblastoma multiforme. It is associated with an improved response to chemotherapy with temozolomide and longer overall survival. MGMT promoter methylation has implications for the clinical course of patients. In recent years, there have been observations of patients changing their MGMT promoter methylation from primary tumor to relapse. Still, data on this topic are scarce. Studies often consist of only few patients and provide rather contrasting results, making it hard to draw a clear conclusion on clinical implications. Here, we summarize the previous publications on this topic, add new cases of changing MGMT status in relapse and finally combine all reports of more than ten patients in a statistical analysis based on the Wilson score interval. MGMT promoter methylation changes are seen in 115 of 476 analyzed patients (24\%; CI: 0.21-0.28). We discuss potential reasons like technical issues, intratumoral heterogeneity and selective pressure of therapy. The clinical implications are still ambiguous and do not yet support a change in clinical practice. However, retesting MGMT methylation might be useful for future treatment decisions and we encourage clinical studies to address this topic},
  language  = {en}
}
@article{AltieriDiDatoModicaetal.2020,
  author    = {Altieri, Barbara and Di Dato, Carla and Modica, Roberta and Bottiglieri, Filomena and Di Sarno, Antonella and Pittaway, James F.H. and Martini, Chiara and Faggiano, Antongiulio and Colao, Annamaria},
  title     = {Bone metabolism and vitamin D implication in gastroenteropancreatic neuroendocrine tumors},
  series = {Nutrients},
  volume    = {12},
  journal   = {Nutrients},
  number    = {4},
  issn      = {2072-6643},
  doi       = {10.3390/nu12041021},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203823},
  year      = {2020},
  abstract  = {Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.},
  language  = {en}
}
@phdthesis{Eujen2010,
  author    = {Eujen, Heike Carola},
  title     = {Blockade der Antigenerkennung als therapeutische Strategie in einem CD8+ T-Zell vermittelten Mausmodell der Multiplen Sklerose},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-52052},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Die Multiple Sklerose (MS) ist eine schwere, momentan noch unheilbare Autoimmunerkrankung des Zentralnervensystems, die weltweit ca. 1 Mio. Menschen betrifft. Da die zur Zeit verf{\"u}gbaren, anti-inflammatorischen und immunsuppressiven Therapieformen lediglich krankheitsverz{\"o}gernd wirken, ist es Gegenstand intensiver Forschungsbem{\"u}hungen, M{\"o}glichkeiten zur spezifischen Interferenz mit bei der MS ablaufenden Pathomechanismen zu ergr{\"u}nden und im Tiermodell zu testen. Das von uns f{\"u}r diese Arbeit verwendete Mausmodell einer CD8+ T-Zell vermittelten Experimentellen Autoimmunen Enzephalomyelitis (EAE) tr{\"a}gt dabei neuen Erkenntnissen Rechnung, die zeigen, dass zytotoxische T-Lymphozyten bei der Pathogenese der humanen MS von entscheidender Bedeutung sind. Es handelt sich um doppelt transgene Nachkommen von M{\"a}usen, die das Modell-Antigen Ovalbumin (OVA) unter der Kontrolle eines Oligodendrozyten (ODC-)-spezifischen MBP-Promotors im ZNS exprimieren, und M{\"a}usen, die Ovalbumin-spezifische CD8+ T-Zellen besitzen (OT-I Zellen). Es kommt in diesem Modell zur Autoantigenerkennung durch die CD8+ T-Zellen mit konsekutiver Ausbildung einer fulminanten, letal verlaufenden EAE. Ziel der vorliegenden Arbeit war es nun, die therapeutische Potenz des monoklonalen Antik{\"o}rpers 25-D1.16 zu evaluieren, der gegen das Autoantigen Ovalbumin in Kombination mit einem MHC-I-Molek{\"u}l gerichtet ist. Mit Hilfe von FACS-Analysen und Fluoreszenz-Mikroskopie konnten wir zun{\"a}chst best{\"a}tigen, dass 25-D1.16 spezifisch den Komplex aus dem Peptid SIINFEKL (antigenes Epitop von Ovalbumin) gebunden an ein MHC-I-Molek{\"u}l (H-2Kb) erkennt. In nachfolgenden in vitro Versuchen wurde der Einfluss des Antik{\"o}rpers auf Aktivierung und Proliferation von durch SIINFEKL:MHC-I-Komplex stimulierten OT-I Zellen untersucht. Es wurden hierf{\"u}r Zellproliferation (Proliferations-Assays), Expression des Oberfl{\"a}chenmolek{\"u}ls CD69 (FACS-Analysen) sowie IFN-γ-Sekretion (ELISA) gemessen. In Gegenwart von 25-D1.16 zeigte sich durchweg eine hochsignifikante Reduktion der jeweiligen Proliferations-/Aktivierungsmarker. Wir konnten somit in vitro zeigen, dass der gegen das Autoantigen Ovalbumin/H-2Kb gerichtete, monoklonale Antik{\"o}rper 25-D1.16 kompetitiv die Aktivierung und Proliferation entsprechender T-Lymphozyten inhibieren kann. Um diese Daten in vivo zu validieren und die pathogenetische Relevanz zu {\"u}berpr{\"u}fen, haben wir ODC-OVA/OT-I doppelt transgenen M{\"a}usen verschiedene Dosen von 25-D1.16 vor Auftreten erster EAE-Symptome einmalig intraperitoneal verabreicht. Anschließend wurde der Krankheitsverlauf klinisch beurteilt. Im EAE-Stadium 4 ohne Besserungstendenz oder bei Versuchsende wurden außerdem histologische Schnitte des Zentralnervensystems angefertigt, gef{\"a}rbt (H.E., CD3, Mac-3, Luxol Fast Blue/PAS) und mit unbehandelten Tieren verglichen. Ein Teil der ODC-OVA/OT-I doppelt transgenen Tiere blieb nach Applikation des Antik{\"o}rpers v{\"o}llig gesund, w{\"a}hrend bei einem anderen Teil der Ausbruch der EAE zwar nicht vollst{\"a}ndig verhindert, ihr Schweregrad aber deutlich gemildert wurde. Der Effekt der Antik{\"o}rpertherapie war jedoch nicht nur klinisch, sondern auch histopathologisch {\"u}berzeugend. So zeigte das Zentralnervensystem erfolgreich therapierter M{\"a}use eine weitgehend bis vollst{\"a}ndig intakte Gewebsarchitektur (H.E.-F{\"a}rbung) mit im Vergleich zu unbehandelten M{\"a}usen drastisch reduzierter OT-I Zell- und Makrophagen/Mikroglia-Infiltration (Immunhistochemie CD3 und Mac-3). In der Luxol Fast Blue/PAS-F{\"a}rbung fanden sich keinerlei Entmarkungsherde sondern durchg{\"a}ngig myelinisierte Axone. Es gelang uns somit durch hohe Antik{\"o}rperdosen (500 μg pro ODC-OVA/OT-I doppelt transgener Maus) bei 83 \% der behandelten Versuchstiere den Ausbruch der EAE ganz zu verhindern bzw. deren Verlauf deutlich abzumildern. Zusammenfassend beschreiben wir hier erstmals die antigen-spezifische Therapie einer CD8+ T-Zell mediierten EAE mittels eines gegen Peptid:MHC-I-Komplex gerichteten, monoklonalen Antik{\"o}rpers. Durch Interferenz mit der Erkennung des Autoantigens durch die CD8+ T-Zellen waren wir in vivo in der Lage, den Pathomechanismus der EAE zu inhibieren. Hieraus ergibt sich ein vielversprechendes Behandlungskonzept f{\"u}r die Therapie der Multiplen Sklerose am Menschen.},
  subject      = {Multiple Sklerose},
  language  = {de}
}
@phdthesis{Jud2010,
  author    = {Jud, Johanna},
  title     = {Benigne Knochentumoren und tumor{\"a}hnliche L{\"a}sionen im Kindesalter - Eine retrospektive Analyse {\"u}ber 14 Jahre},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-52005},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Benigne Knochentumoren und tumor{\"a}hnliche L{\"a}sionen sind insgesamt sehr seltene Erkrankungen und machen weniger als 1\% aller Tumoren aus. Trotz dieser Seltenheit weisen sie mit mehr als 100 verschiedenen Entit{\"a}ten eine extreme Vielfalt auf. In der vorliegenden Arbeit wurden die Daten von 68 Patienten erfasst, die in einem Zeitraum von mehr als 14 Jahren (1993-2007) aufgrund eines benignen Knochentumors oder einer tumor{\"a}hnlichen L{\"a}sion in der kinderchirurgischen Abteilung der Universit{\"a}tsklinik W{\"u}rzburg behandelt wurden. Die erfassten Daten wurden im Hinblick auf die epidemiologischen Daten wie H{\"a}ufigkeit, Alter, Geschlecht und Lokalisation sowie besonders im Hinblick auf diagnostische und therapeutische Vorgehensweisen sowie auf die Rezidivh{\"a}ufigkeit ausgewertet. Die h{\"a}ufigsten benignen Knochentumoren in unserer Erhebung stellten das Osteochondrom (39\%) und die juvenile Knochenzyste (38\%) dar, gefolgt von der aneurysmatischen Knochenzyste (9\%), der fibr{\"o}sen Dysplasie (7\%) und dem eosinophilen Granulom (4\%). Das Enchondrom, der fibr{\"o}se Kortikalisdefekt und das nicht ossifizierende Fibrom traten jeweils lediglich in 1\% der F{\"a}lle auf. 58,8\% der Tumoren waren in der Altersgruppe der 10- bis 18- J{\"a}hrigen zu finden und das Geschlechterverh{\"a}ltnis von ♀:♂ betrug 1:1,43. Die meisten L{\"a}sionen waren in den langen R{\"o}hrenknochen zu finden, n{\"a}mlich im Humerus (36\%), im Femur (19\%) und in den Unterschenkelknochen (23\%). In unserer Studie wurden die benignen Knochentumoren und tumor{\"a}hnlichen L{\"a}sionen in 37\% der F{\"a}lle mit Exkochleation behandelt, in 24\% mit Prevot- Nagelung, in 18\% mit Cortisoninstillation und in 15\% mit K{\"u}rettage mit anschließender Spongiosaf{\"u}llung. Bei den restlichen 6\% wurde eine K{\"u}rettage ohne Spongiosaf{\"u}llung durchgef{\"u}hrt. Die Rezidivrate lag bei unserer Erhebung insgesamt bei 13,2\%. Hierbei war auff{\"a}llig, dass bei den ≤3- J{\"a}hrigen signifikant h{\"a}ufiger Rezidive auftraten als bei den 4- bis 18- J{\"a}hrigen. Ebenso war der Radius von Rezidiven prozentual h{\"a}ufiger betroffen (33,3\%) als Humerus (16,7\%), Unterschenkel (13,3\%) und Femur (7,7\%). Im Bezug auf das angewandte Therapieverfahren kam es nach Cortisoninstillation signifikant h{\"a}ufiger (41,7\%) zu Rezidiven als nach den anderen Operationen (3,8\%-20\%). In 5,88\% der F{\"a}lle traten nach Operation Komplikationen auf. In keinem der 68 F{\"a}lle wurden im gesamten Verlauf Anzeichen f{\"u}r eine maligne Entartung gefunden. Ein Vergleich mit den Angaben in der internationalen Literatur f{\"u}hrte in fast allen Bereichen zu weitgehender {\"U}bereinstimmung. Hervorgehoben werden sollen an dieser Stelle jedoch die Ergebnisse unserer Studie im Bezug auf die juvenile Knochenzyste. Auch hier zeigte sich ein signifikanter Unterschied beim Vergleich der Rezidivraten der ≤3- J{\"a}hrigen mit der der 4- bis 18- J{\"a}hrigen. Außerdem war die Rezidivquote nach Cortisoninstillation mit 50\% signifikant h{\"o}her als die nach Prevot-Nagelung und nach K{\"u}rettage mit Spongiosaf{\"u}llung (jeweils 0\%). Im Hinblick auf diese exorbitante Rezidivquote nach Cortisonistillation und nach Abw{\"a}gung weiterer Faktoren wie Morbidit{\"a}t, Mobilit{\"a}t, Hospitalisation und Kosten stellt unserer Meinung nach die Prevot-Nagelung bei der Behandlung der juvenilen Knochenzyste die bessere Alternative dar.},
  subject      = {Knochentumor},
  language  = {de}
}
@article{SalingerHuLiuetal.2018,
  author    = {Salinger, Tim and Hu, Kai and Liu, Dan and Taleh, Scharoch and Herrmann, Sebastian and Oder, Daniel and Gensler, Daniel and M{\"u}ntze, Jonas and Ertl, Georg and Lorenz, Kristina and Frantz, Stefan and Weidemann, Frank and Nordbeck, Peter},
  title     = {Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis},
  series = {Cardiology Research and Practice},
  journal   = {Cardiology Research and Practice},
  doi       = {10.1155/2018/3713897},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227291},
  pages     = {3713897, 1-7},
  year      = {2018},
  abstract  = {Background. Fast progression of the transaortic mean gradient (P-mean) is relevant for clinical decision making of valve replacement in patients with moderate and severe aortic stenosis (AS) patients. However, there is currently little knowledge regarding the determinants affecting progression of transvalvular gradient in AS patients. Methods. This monocentric retrospective study included consecutive patients presenting with at least two transthoracic echocardiography examinations covering a time interval of one year or more between April 2006 and February 2016 and diagnosed as moderate or severe aortic stenosis at the final echocardiographic examination. Laboratory parameters, medication, and prevalence of eight known cardiac comorbidities and risk factors (hypertension, diabetes, coronary heart disease, peripheral artery occlusive disease, cerebrovascular disease, renal dysfunction, body mass index >= 30 Kg/m(2), and history of smoking) were analyzed. Patients were divided into slow (P-mean < 5 mmHg/year) or fast (P-mean >= 5 mmHg/year) progression groups. Results. A total of 402 patients (mean age 78 +/- 9.4 years, 58\% males) were included in the study. Mean follow-up duration was 3.4 +/- 1.9 years. The average number of cardiac comorbidities and risk factors was 3.1 +/- 1.6. Average number of cardiac comorbidities and risk factors was higher in patients in slow progression group than in fast progression group (3.3 +/- 1.5 vs 2.9 +/- 1.7; P = 0.036). Patients in slow progression group had more often coronary heart disease (49.2\% vs 33.6\%; P = 0.003) compared to patients in fast progression group. LDL-cholesterol values were lower in the slow progression group (100 +/- 32.6 mg/dl vs 110.8 +/- 36.6 mg/dl; P = 0.005). Conclusion. These findings suggest that disease progression of aortic valve stenosis is faster in patients with fewer cardiac comorbidities and risk factors, especially if they do not have coronary heart disease. Further prospective studies are warranted to investigate the outcome of patients with slow versus fast progression of transvalvular gradient with regards to comorbidities and risk factors.},
  language  = {en}
}
@phdthesis{Wallstein2011,
  author    = {Wallstein, Rebecca},
  title     = {Artemisinin-Derivate in S{\"u}d-West Nigeria - Gesundheitsverhalten, Therapiestrategien, Verf{\"u}gbarkeit und Qualit{\"a}t},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65600},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Im Rahmen der Zusammenarbeit des Missions{\"a}rztlichen Instituts in W{\"u}rzburg mit dem Sacred Heart Hospital (Nigeria) wurden vor Ort im Hinblick auf das Problem der Arzneimittelf{\"a}lschungen in Nigeria und dem Auftreten von einzelnen Resistenzen gegen Artemisinin-Derivate Untersuchungen bez{\"u}glich der aktuellen Situation im Kampf gegen Malaria im Großraum Abeokuta durchgef{\"u}hrt. Der Kenntnisstand {\"u}ber Malaria und das Gesundheitsverhalten einer f{\"u}r die nigerianische Bev{\"o}lkerung m{\"o}glichst repr{\"a}sentativen Probandengruppe (n=100) wurden mithilfe eines Fragebogens erfasst. Ebenfalls mithilfe eines Fragebogens wurden die Therapiestrategien der einheimischen {\"A}rzte (n=34) gegen Malaria untersucht und die Verf{\"u}gbarkeit und Qualit{\"a}t von Artemisinin- Derivaten im Untersuchungsgebiet durch den Erwerb von Medikamenten-Samples (n=29) und anschließende Labortests {\"u}berpr{\"u}ft. Die Befragung der Bev{\"o}lkerung ergab, dass Wissen bez{\"u}glich der Ursachen, Symptome und Pr{\"a}vention der Malaria durchaus vorhanden ist, wobei große Unterschiede abh{\"a}ngig vom Bildungsstand bestanden. Vor allem {\"a}ltere Menschen verf{\"u}gten {\"u}ber wesentlich geringere Schulbildung und verließen sich deshalb sehr viel mehr auf die traditionelle Medizin. Dar{\"u}ber hinaus war eine oftmalige Bagatellisierung der Malaria auff{\"a}llig, weshalb viele Probanden (53\%) sich im Krankheitsfall gegen das Aufsuchen eines Krankenhauses entschieden. Die Befragung bez{\"u}glich der Therapiestrategien der einheimischen {\"A}rzte zeigte, dass die Richtlinien der WHO bez{\"u}glich der Verwendung von ACT offensichtlich optimal angenommen und angewandt werden. Als m{\"o}gliches Problem stellte sich die von 76,7\% der {\"A}rzte nur selten angewandte Labordiagnostik dar, eine Tatsache, die Fehldiagnosen beg{\"u}nstigt. Bei der Testung der Medikamente erwiesen sich 14,3\% der Proben als minderwertig oder sogar gef{\"a}lscht, was offiziellen Angaben entspricht. Zudem handelte es sich bei 37,9\% der Arzneimittelproben um Monopr{\"a}parate, was im Hinblick auf Resistenzbildung mehr als bedenklich ist. Diese Resultate weisen darauf hin, dass im S{\"u}dwesten Nigerias die Malaria-Problematik noch immer nicht ad{\"a}quat gel{\"o}st ist. Immer noch erhalten viel zu wenige Menschen eine optimale Therapie, was zu einem großen Teil an fehlendem Wissen und damit verbundenem falschem Gesundheitsverhalten, an dem großen Einfluss der traditionellen Medizin und an der Pr{\"a}senz von gef{\"a}lschten, wirkungslosen Arzneimitteln auf dem Markt liegt.},
  subject      = {Malaria},
  language  = {de}
}
@article{RiedmeierDecarolisHaubitzetal.2021,
  author    = {Riedmeier, Maria and Decarolis, Boris and Haubitz, Imme and M{\"u}ller, Sophie and Uttinger, Konstantin and B{\"o}rner, Kevin and Reibetanz, Joachim and Wiegering, Armin and H{\"a}rtel, Christoph and Schlegel, Paul-Gerhardt and Fassnacht, Martin and Wiegering, Verena},
  title     = {Adrenocortical carcinoma in childhood: a systematic review},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {21},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13215266},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248507},
  year      = {2021},
  abstract  = {Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65\% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80\% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89\%). Most patients were diagnosed with localized disease, whereas 23\% had metastasis at primary diagnosis. Only 72\% of the patients achieved complete resection. In 334 children (23\%), recurrent disease was reported: 81\% — local recurrence, 19\% (n = 65) — distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.},
  language  = {en}
}
@article{UttingerRiedmeierReibetanzetal.2022,
  author    = {Uttinger, Konstantin L. and Riedmeier, Maria and Reibetanz, Joachim and Meyer, Thomas and Germer, Christoph Thomas and Fassnacht, Martin and Wiegering, Armin and Wiegering, Verena},
  title     = {Adrenalectomies in children and adolescents in Germany - a diagnose related groups based analysis from 2009-2017},
  series = {Frontiers in Endocrinology},
  volume    = {13},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2022.914449},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282280},
  year      = {2022},
  abstract  = {Background Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome. Methods This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included. Results A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1\%). The majority of patients were between 0 and 5 years old (52\% overall), while 11.1\% were between 6 and 11 and 38.8\% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56\%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29\% of all cases with the majority of affected patients being 12 years or older. 15\% were not defined regarding tumor behavior. Overall complication rate was 27\% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different "low volume" hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different "high volume" hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications. Conclusion Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals.},
  language  = {en}
}