TY - JOUR A1 - Kraemer, Markus A1 - Becker, Jana A1 - Bley, Thorsten Alexander A1 - Steinbrecher, Andreas A1 - Minnerup, Jens A1 - Hellmich, Bernhard T1 - Diagnostik und Therapie der Riesenzellarteriitis T1 - Diagnostics and treatment of giant cell arteritis JF - Der Nervenarzt N2 - Die Riesenzellarteriitis (RZA) ist in der Altersgruppe der über 50-Jährigen die häufigste idiopathische systemische Vaskulitis. Die Erkrankung bedarf einer zeitnahen Diagnostik und Therapie, um schwere Komplikationen wie eine Erblindung oder einen Schlaganfall zu vermeiden. Die Rezidivneigung erfordert eine mehrjährige, zum Teil lebenslange Glukokortikoid(GC)-Therapie, was das Risiko GC-induzierter Langzeitnebenwirkungen erhöht. Daher wird bei der Mehrzahl der Patienten eine additive GC-einsparende Therapie empfohlen. Hierzu steht der Anti-IL-6-Rezeptor-Antikörper Tocilizumab in subkutaner Applikation als zugelassene Substanz zur Verfügung, alternativ kann Methotrexat (MTX) eingesetzt werden (off-label). N2 - Giant cell arteritis (GCA) is the most common idiopathic systemic vasculitis in the age group over 50 years. It requires prompt diagnostics and treatment to avoid severe complications, such as visual loss or stroke. The tendency to relapse makes a glucocorticoid (GC) treatment necessary for several years and sometimes lifelong, which increases the risk of GC-induced long-term side effects. Therefore, additive GC-sparing treatment is recommended in the majority of patients. For this purpose, the anti-IL‑6 receptor antibody tocilizumab is available as an approved substance for subcutaneous application; alternatively, methotrexate (MTX) can be used (off-label). KW - Riesenzellarteriitis KW - Diagnose KW - Therapie KW - Glukokortikoide KW - Glukokortikoideinsparende Therapie KW - Tocilizumab KW - Methotrexat KW - giant cell arteritis KW - diagnosis KW - therapy KW - glucocorticoids KW - glucocorticoid-sparing agents KW - Tocilizumab KW - Methotrexate Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307771 SN - 0028-2804 SN - 1433-0407 VL - 93 IS - 8 ER - TY - JOUR A1 - Riederer, Peter A1 - ter Meulen, Volker T1 - Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses JF - Journal of Neural Transmission N2 - 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. KW - coronavirus KW - COVID-19 KW - SARS-CoV-2 brain disorders KW - cardiorespiratory centre KW - brain pathology KW - neurological symptoms/disorders KW - brain stem KW - Parkinson’s disease KW - Parkinsonism KW - Alzheimer’s disease KW - multiple sclerosis KW - movement disorders KW - neuroinvasion KW - therapy KW - neuroprotection KW - depression KW - cognitive dysfunction KW - brain bank KW - postmortem studies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-314637 SN - 0300-9564 SN - 1435-1463 VL - 127 IS - 9 ER - TY - JOUR A1 - Schulmeyer, Carla E. A1 - Fasching, Peter A. A1 - Häberle, Lothar A1 - Meyer, Julia A1 - Schneider, Michael A1 - Wachter, David A1 - Ruebner, Matthias A1 - Pöschke, Patrik A1 - Beckmann, Matthias W. A1 - Hartmann, Arndt A1 - Erber, Ramona A1 - Gass, Paul T1 - Expression of the immunohistochemical markers CK5, CD117, and EGFR in molecular subtypes of breast cancer correlated with prognosis JF - Diagnostics N2 - 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. KW - early breast cancer KW - therapy KW - prognosis KW - CK5 KW - CD117 KW - EGFR KW - triple-negative breast cancer Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304987 SN - 2075-4418 VL - 13 IS - 3 ER - TY - JOUR A1 - Esmaeilpour, Donya A1 - Broscheit, Jens Albert A1 - Shityakov, Sergey T1 - Cyclodextrin-based polymeric materials bound to corona protein for theranostic applications JF - International Journal of Molecular Sciences N2 - 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. KW - cyclodextrin KW - theranostics KW - protein corona KW - nanomedicine KW - therapy KW - polymers Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297399 SN - 1422-0067 VL - 23 IS - 21 ER - TY - JOUR A1 - Feldheim, Jonas A1 - Kessler, Almuth F. A1 - Feldheim, Julia J. A1 - Schulz, Ellina A1 - Wend, David A1 - Lazaridis, Lazaros A1 - Kleinschnitz, Christoph A1 - Glas, Martin A1 - Ernestus, Ralf-Ingo A1 - Brandner, Sebastian A1 - Monoranu, Camelia M. A1 - Löhr, Mario A1 - Hagemann, Carsten T1 - Effects of long-term temozolomide treatment on glioblastoma and astrocytoma WHO grade 4 stem-like cells JF - International Journal of Molecular Sciences N2 - 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. KW - glioblastoma KW - astrocytoma KW - IDH KW - MGMT KW - therapy KW - temozolomide KW - cancer stem cells Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284417 SN - 1422-0067 VL - 23 IS - 9 ER - TY - JOUR A1 - Strobel, Katharina A1 - Sickenberger, Christina A1 - Schoen, Christoph A1 - Kneitz, Hermann A1 - Kolb-Mäurer, Annette A1 - Goebeler, Matthias T1 - Diagnosis and therapy of Mycobacterium marinum: a single-center 21-year retrospective analysis JF - Journal der Deutschen Dermatologischen Gesellschaft N2 - 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 Würzburg 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. KW - Mycobacterium marinum KW - diagnosis KW - therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318428 VL - 20 IS - 9 SP - 1211 EP - 1218 ER - TY - JOUR A1 - Schummer, Patrick A1 - Schilling, Bastian T1 - How representative are data from global trials on programmed death-1 blockade in melanoma? JF - The British Journal of Dermatology KW - programmed cell death receptor-1 KW - melanoma KW - therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318406 VL - 187 IS - 3 SP - 283 EP - 284 ER - TY - JOUR A1 - Riedmeier, Maria A1 - Decarolis, Boris A1 - Haubitz, Imme A1 - Müller, Sophie A1 - Uttinger, Konstantin A1 - Börner, Kevin A1 - Reibetanz, Joachim A1 - Wiegering, Armin A1 - Härtel, Christoph A1 - Schlegel, Paul-Gerhardt A1 - Fassnacht, Martin A1 - Wiegering, Verena T1 - Adrenocortical carcinoma in childhood: a systematic review JF - Cancers N2 - 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. KW - pediatric adrenocortical cancer KW - pediatric adrenocortical adenoma KW - pediatric adrenocortical tumor KW - prognostic factors KW - therapy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248507 SN - 2072-6694 VL - 13 IS - 21 ER - TY - JOUR A1 - Wiegering, Verena A1 - Riedmeier, Maria A1 - Thompson, Lester D. R. A1 - Virgone, Calogero A1 - Redlich, Antje A1 - Kuhlen, Michaela A1 - Gultekin, Melis A1 - Yalcin, Bilgehan A1 - Decarolis, Boris A1 - Härtel, Christoph A1 - Schlegel, Paul-Gerhardt A1 - Fassnacht, Martin A1 - Timmermann, Beate T1 - Radiotherapy for pediatric adrenocortical carcinoma - Review of the literature JF - Clinical and Translational Radiation Oncology N2 - 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. KW - pediatric adrenocortical cancer KW - pediatric adrenocortical carcinoma KW - pediatric adrenocortical tumor KW - radiotherapy KW - therapy KW - treatment Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300472 VL - 35 ER - TY - JOUR A1 - Salinger, Tim A1 - Hu, Kai A1 - Liu, Dan A1 - Taleh, Scharoch A1 - Herrmann, Sebastian A1 - Oder, Daniel A1 - Gensler, Daniel A1 - Müntze, Jonas A1 - Ertl, Georg A1 - Lorenz, Kristina A1 - Frantz, Stefan A1 - Weidemann, Frank A1 - Nordbeck, Peter T1 - Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis JF - Cardiology Research and Practice N2 - 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. KW - Valvular heart-desease KW - Prognostic impact KW - Risk-factors KW - Chronic heart-failure KW - Prevalence KW - mild KW - statins KW - therapy KW - mortality Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227291 ER -