@article{BoeckMaurusGerhardHartmannetal.2023, author = {B{\"o}ck, Julia and Maurus, Katja and Gerhard-Hartmann, Elena and Br{\"a}ndlein, Stephanie and Kurz, Katrin S. and Ott, German and Anagnostopoulos, Ioannis and Rosenwald, Andreas and Zam{\`o}, Alberto}, title = {Targeted panel sequencing in the routine diagnosis of mature T- and NK-cell lymphomas}, series = {Frontiers in Oncology}, volume = {13}, journal = {Frontiers in Oncology}, issn = {2234-943X}, doi = {10.3389/fonc.2023.1231601}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326478}, year = {2023}, abstract = {Diagnosing any of the more than 30 types of T-cell lymphomas is considered a challenging task for many pathologists and currently requires morphological expertise as well as the integration of clinical data, immunophenotype, flow cytometry and clonality analyses. Even considering all available information, some margin of doubt might remain using the current diagnostic procedures. In recent times, the genetic landscape of most T-cell lymphomas has been elucidated, showing a number of diagnostically relevant mutations. In addition, recent data indicate that some of these genetic alterations might bear prognostic and predictive value. Extensive genetic analyses, such as whole exome or large panel sequencing are still expensive and time consuming, therefore limiting their application in routine diagnostic. We therefore devoted our effort to develop a lean approach for genetic analysis of T-cell lymphomas, focusing on maximum efficiency rather than exhaustively covering all possible targets. Here we report the results generated with our small amplicon-based panel that could be used routinely on paraffin-embedded and even decalcified samples, on a single sample basis in parallel with other NGS-panels used in our routine diagnostic lab, in a relatively short time and with limited costs. We tested 128 available samples from two German reference centers as part of our routine work up (among which 116 T-cell lymphomas), which is the largest routine diagnostic series reported to date. Our results showed that this assay had a very high rate of technical success (97\%) and could detect mutations in the majority (79\%) of tested T-cell lymphoma samples.}, language = {en} } @phdthesis{Frommer2024, author = {Frommer, Vivien Isabel}, title = {Korrelation von Bruxismus mit psychosozialen und anamnestischen Parametern}, doi = {10.25972/OPUS-34687}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346874}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Zweck: Obwohl Bruxismus im Wesentlichen als Verhalten mit multifaktorieller Genese gilt, konnten bisher nicht eindeutig die damit assoziierten Komorbidit{\"a}ten aufgekl{\"a}rt werden. Die Zielsetzung war, anamnestische und psychosoziale Unterschiede zwischen Proband(inn)en mit und ohne m{\"o}glichem bzw. definitivem Bruxismus zu ermitteln. Dar{\"u}ber hinaus sollte die {\"U}bereinstimmung verschiedener Instrumente zur Bruxismus-Diagnostik und der Effekt von zwei Interventionen (bedingte elektrische Stimulation (CES) und Kautraining) analysiert werden. Methoden: In dieser klinischen, explorativen Studie wurden 76 Proband(inn)en untersucht. Die Proband(inn)en wurden in die drei Gruppen Kontrollgruppe, aktive Interventionsgruppe und Rehabite Interventionsgruppe eingeteilt. Die Kontrollgruppe trug ein portables EMG-Ger{\"a}t (GrindCare) jede Nacht {\"u}ber einen Beobachtungszeitraum von 5 Wochen inaktiv. Die aktive Interventionsgruppe trug es die erste Woche inaktiv, dann 2 Wochen aktiv mit CES und anschließend erneut 2 Wochen inaktiv. Die RehaBite Interventionsgruppe verwendete das GrindCare eine Woche inaktiv, darauf folgte ein zweiw{\"o}chiges Kautraining mit einer Bissgabel namens RehaBite aber ohne EMG-Begleitung und die letzten zwei Wochen verliefen ohne Rehabite und GrindCare. Zu Beginn und am Ende des Beobachtungszeitraums f{\"u}llten alle drei Gruppen die gleichen Frageb{\"o}gen, u.a. die Oral Behavior Checklist (OBC) und verschiedene Frageb{\"o}gen zu k{\"o}rperlichen und psychologischen Parametern, aus. Das GrindCare misst die Episoden und erm{\"o}glicht damit die Diagnose eines definitiven Schafbruxismus (SB). Ergebnisse: Es existierten signifikante Unterschiede zwischen Proband(inn)en mit und ohne Bruxismus (m{\"o}glicher und definitiver SB, m{\"o}glicher Wachbruxismus (WB), m{\"o}glicher kombinierter SB und WB) in diversen anamnestischen und psychosozialen Parametern. Außerdem bestand ein signifikanter Zusammenhang zwischen erh{\"o}hter Kieferaktivit{\"a}t (diagnostiziert mittels OBC) und SB- sowie WB-Selbstangabe sowie zwischen den Selbstangaben von SB und WB untereinander, nicht jedoch zwischen Frageb{\"o}gen und apparativer Diagnostik. Die CES bewirkte keine Reduktion der Episoden, daf{\"u}r verbesserten sich jedoch einzelne k{\"o}rperliche und psychosoziale Parameter in der aktiven bzw. in der Rehabite Gruppe im Laufe des Beobachtungszeitraums. Fazit: Personen mit und ohne m{\"o}glichem bzw. definitivem Bruxismus unterschieden sich in verschiedenen anamnestischen, k{\"o}rperlichen und psychosozialen Eigenschaften voneinander. Außerdem bestehen signifikante Korrelationen zwischen SB und WB laut Selbstangabe, nicht jedoch bez{\"u}glich der apparativen Bruxismus-Diagnostik mit dem GrindCare. W{\"a}hrend die Episoden nicht durch die CES gesenkt wurden, verringerten sich -eventuell durch RehaBite bzw. CES bedingt- bestimmte Beschwerden. Weiterer Forschungsbedarf besteht, um auf der Basis gr{\"o}ßerer Stichproben die gefundenen Auff{\"a}lligkeiten statistisch abzusichern.}, subject = {Bruxismus}, language = {de} } @article{SchreglmannBurkeBatlaetal.2022, author = {Schreglmann, Sebastian R. and Burke, Derek and Batla, Amit and Kresojevic, Nikola and Wood, Nicholas and Heales, Simon and Bhatia, Kailash P.}, title = {Cerebellar and Midbrain Lysosomal Enzyme Deficiency in Isolated Dystonia}, series = {Movement Disorders}, volume = {37}, journal = {Movement Disorders}, number = {4}, doi = {10.1002/mds.28937}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318743}, pages = {875 -- 877}, year = {2022}, language = {en} } @article{WhiteSpringerWiseetal.2022, author = {White, P. Lewis and Springer, Jan and Wise, Matt P. and Einsele, Hermann and L{\"o}ffler, Claudia and Seif, Michelle and Prommersberger, Sabrina and Backx, Matthijs and L{\"o}ffler, J{\"u}rgen}, title = {A clinical case of COVID-19-associated pulmonary aspergillosis (CAPA), illustrating the challenges in diagnosis (despite overwhelming mycological evidence)}, series = {Journal of Fungi}, volume = {8}, journal = {Journal of Fungi}, number = {1}, issn = {2309-608X}, doi = {10.3390/jof8010081}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-302438}, year = {2022}, abstract = {The COVID-19 pandemic has resulted in large numbers of patients requiring critical care management. With the established association between severe respiratory virus infection and invasive pulmonary aspergillosis (7.6\% for COVID-19-associated pulmonary aspergillosis (CAPA)), the pandemic places a significant number of patients at potential risk from secondary invasive fungal disease. We described a case of CAPA with substantial supporting mycological evidence, highlighting the need to employ strategic diagnostic algorithms and weighted definitions to improve the accuracy in diagnosing CAPA.}, language = {en} } @article{HendricksLenschowKroissetal.2021, author = {Hendricks, Anne and Lenschow, Christina and Kroiss, Matthias and Buck, Andreas and Kickuth, Ralph and Germer, Christoph-Thomas and Schlegel, Nicolas}, title = {Evaluation of diagnostic efficacy for localization of parathyroid adenoma in patients with primary hyperparathyroidism undergoing repeat surgery}, series = {Langenbeck's Archives of Surgery}, volume = {406}, journal = {Langenbeck's Archives of Surgery}, number = {5}, issn = {1435-2451}, doi = {10.1007/s00423-021-02191-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267520}, pages = {1615-1624}, year = {2021}, abstract = {Purpose Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse. Methods A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated. Results Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9\%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100\%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80\%. Conclusion These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT.}, 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{ZinnerSperlichKruegeretal.2015, author = {Zinner, Christoph and Sperlich, Billy and Krueger, Malte and Focke, Tim and Reed, Jennifer and Mester, Joachim}, title = {Strength, Endurance, Throwing Velocity and in-Water Jump Performance of Elite German Water Polo Players}, series = {Journal of Human Kinetics}, volume = {45}, journal = {Journal of Human Kinetics}, doi = {10.1515/hukin-2015-0015}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148812}, pages = {149-156}, year = {2015}, abstract = {The purpose of this study was threefold: 1) to assess the eggbeater kick and throwing performance using a number of water polo specific tests, 2) to explore the relation between the eggbeater kick and throwing performance, and 3) to investigate the relation between the eggbeater kick in the water and strength tests performed in a controlled laboratory setting in elite water polo players. Fifteen male water polo players of the German National Team completed dynamic and isometric strength tests for muscle groups (adductor, abductor, abdominal, pectoralis) frequently used during water polo. After these laboratory strength tests, six water polo specific in-water tests were conducted. The eggbeater kick assessed leg endurance and agility, maximal throwing velocity and jump height. A 400 m test and a sprint test examined aerobic and anaerobic performance. The strongest correlation was found between jump height and arm length (p < 0.001, r = 0.89). The laboratory diagnostics of important muscles showed positive correlations with the results of the in-water tests (p < 0.05, r = 0.52-0.70). Muscular strength of the adductor, abdominal and pectoralis muscles was positively related to in-water endurance agility as assessed by the eggbeater kick (p < 0.05; r = 0.53-0.66). Findings from the current study emphasize the need to assess indices of water polo performance both in and out of the water as well as the relation among these parameters to best assess the complex profile of water polo players.}, language = {en} }