@article{FeketeEgbertsPreissleretal.2021, author = {Fekete, Stefanie and Egberts, K. and Preissler, T. and Wewetzer, C. and Mehler-Wex, C. and Romanos, M. and Gerlach, M.}, title = {Estimation of a preliminary therapeutic reference range for children and adolescents with tic disorders treated with tiapride}, series = {European Journal of Clinical Pharmacology}, volume = {77}, journal = {European Journal of Clinical Pharmacology}, number = {2}, doi = {10.1007/s00228-020-03000-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279893}, pages = {163-170}, year = {2021}, abstract = {Purpose Tiapride is commonly used in Europe for the treatment of tics. The aim of this study was to examine the relationship between dose and serum concentrations of tiapride and potential influential pharmacokinetic factors in children and adolescents. In addition, a preliminary therapeutic reference range for children and adolescents with tics treated with tiapride was calculated. Methods Children and adolescents treated with tiapride at three university hospitals and two departments of child and adolescents psychiatry in Germany and Austria were included in the study. Patient characteristics, doses, serum concentrations, and therapeutic outcome were assessed during clinical routine care using standardised measures. Results In the 49 paediatric patients (83.7\% male, mean age = 12.5 years), a positive correlation was found between tiapride dose (median 6.9 mg/kg, range 0.97-19.35) and serum concentration with marked inter-individual variability. The variation in dose explained 57\% of the inter-patient variability in tiapride serum concentrations; age, gender, and concomitant medication did not contribute to the variability. The symptoms improved in 83.3\% of the patients. 27.1\% of the patients had mild or moderate ADRs. No patient suffered from severe ADRs. Conclusions This study shows that tiapride treatment was effective and safe in most patients with tics. Compared with the therapeutic concentration range established for adults with Chorea Huntington, our data hinted at a lower lower limit (560 ng/ml) and similar upper limit (2000 ng/ml).}, language = {en} } @article{GuthHueserRothetal.2021, author = {Guth, Sabine and H{\"u}ser, Stephanie and Roth, Angelika and Degen, Gisela and Diel, Patrick and Edlund, Karolina and Eisenbrand, Gerhard and Engel, Karl-Heinz and Epe, Bernd and Grune, Tilman and Heinz, Volker and Henle, Thomas and Humpf, Hans-Ulrich and J{\"a}ger, Henry and Joost, Hans-Georg and Kulling, Sabine E. and Lampen, Alfonso and Mally, Angela and Marchan, Rosemarie and Marko, Doris and M{\"u}hle, Eva and Nitsche, Michael A. and R{\"o}hrdanz, Elke and Stadler, Richard and van Thriel, Christoph and Vieths, Stefan and Vogel, Rudi F. and Wascher, Edmund and Watzl, Carsten and N{\"o}thlings, Ute and Hengstler, Jan G.}, title = {Contribution to the ongoing discussion on fluoride toxicity}, series = {Archives of Toxicology}, volume = {95}, journal = {Archives of Toxicology}, number = {7}, issn = {0340-5761}, doi = {10.1007/s00204-021-03072-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307161}, pages = {2571-2587}, year = {2021}, abstract = {Since the addition of fluoride to drinking water in the 1940s, there have been frequent and sometimes heated discussions regarding its benefits and risks. In a recently published review, we addressed the question if current exposure levels in Europe represent a risk to human health. This review was discussed in an editorial asking why we did not calculate benchmark doses (BMD) of fluoride neurotoxicity for humans. Here, we address the question, why it is problematic to calculate BMDs based on the currently available data. Briefly, the conclusions of the available studies are not homogeneous, reporting negative as well as positive results; moreover, the positive studies lack control of confounding factors such as the influence of well-known neurotoxicants. We also discuss the limitations of several further epidemiological studies that did not meet the inclusion criteria of our review. Finally, it is important to not only focus on epidemiological studies. Rather, risk analysis should consider all available data, including epidemiological, animal, as well as in vitro studies. Despite remaining uncertainties, the totality of evidence does not support the notion that fluoride should be considered a human developmental neurotoxicant at current exposure levels in European countries.}, language = {en} } @article{PinkawaAebersoldBoehmeretal.2021, author = {Pinkawa, Michael and Aebersold, Daniel M. and B{\"o}hmer, Dirk and Flentje, Michael and Ghadjar, Pirus and Schmidt-Hegemann, Nina-Sophie and H{\"o}cht, Stefan and H{\"o}lscher, Tobias and M{\"u}ller, Arndt-Christian and Niehoff, Peter and Sedlmayer, Felix and Wolf, Frank and Zamboglou, Constantinos and Zips, Daniel and Wiegel, Thomas}, title = {Radiotherapy in nodal oligorecurrent prostate cancer}, series = {Strahlentherapie und Onkologie}, volume = {197}, journal = {Strahlentherapie und Onkologie}, number = {7}, issn = {0179-7158}, doi = {10.1007/s00066-021-01778-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307763}, pages = {575-580}, year = {2021}, abstract = {Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90\% within a follow-up of 1-2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.}, language = {en} } @article{BarileBerryBlaauboeretal.2021, author = {Barile, Frank A. and Berry, Colin and Blaauboer, Bas and Boobis, Alan and Bolt, Herrmann M. and Borgert, Christopher and Dekant, Wolfgang and Dietrich, Daniel and Domingo, Jose L. and Galli, Corrado L. and Gori, Gio Batta and Greim, Helmut and Hengstler, Jan G. and Heslop-Harrison, Pat and Kacew, Sam and Marquardt, Hans and Mally, Angela and Pelkonen, Olavi and Savolainen, Kai and Testai, Emanuela and Tsatsakis, Aristides and Vermeulen, Nico P.}, title = {The EU chemicals strategy for sustainability: in support of the BfR position}, series = {Archives of Toxicology}, volume = {95}, journal = {Archives of Toxicology}, number = {9}, issn = {0340-5761}, doi = {10.1007/s00204-021-03125-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307154}, pages = {3133-3136}, year = {2021}, abstract = {The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved. A continuous process of improvement in consumer protection is clearly desirable but any initiative directed towards this objective must be based on scientific knowledge. It must not confound risk with other factors in determining policy. This conclusion is fully supported in the present Commentary including the request to improve both, data collection and the time-consuming and bureaucratic procedures that delay the publication of regulations.}, language = {en} } @article{DornHerzberg2021, author = {Dorn, Franziska and Herzberg, Moriz}, title = {Response to Letter to the Editor "Keeping Late Thrombectomy Imaging Protocols Simple to Avoid Analysis Paralysis"}, series = {Clinical Neuroradiology}, volume = {31}, journal = {Clinical Neuroradiology}, number = {3}, issn = {1869-1439}, doi = {10.1007/s00062-021-01091-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307023}, pages = {813-814}, year = {2021}, language = {en} } @article{PennigHoyerKrauskopfetal.2021, author = {Pennig, Lenhard and Hoyer, Ulrike Cornelia Isabel and Krauskopf, Alexandra and Shahzad, Rahil and J{\"u}nger, Stephanie T. and Thiele, Frank and Laukamp, Kai Roman and Grunz, Jan-Peter and Perkuhn, Michael and Schlamann, Marc and Kabbasch, Christoph and Borggrefe, Jan and Goertz, Lukas}, title = {Deep learning assistance increases the detection sensitivity of radiologists for secondary intracranial aneurysms in subarachnoid hemorrhage}, series = {Neuroradiology}, volume = {63}, journal = {Neuroradiology}, number = {12}, issn = {0028-3940}, doi = {10.1007/s00234-021-02697-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308117}, pages = {1985-1994}, year = {2021}, abstract = {Purpose To evaluate whether a deep learning model (DLM) could increase the detection sensitivity of radiologists for intracranial aneurysms on CT angiography (CTA) in aneurysmal subarachnoid hemorrhage (aSAH). Methods Three different DLMs were trained on CTA datasets of 68 aSAH patients with 79 aneurysms with their outputs being combined applying ensemble learning (DLM-Ens). The DLM-Ens was evaluated on an independent test set of 104 aSAH patients with 126 aneuryms (mean volume 129.2 ± 185.4 mm3, 13.0\% at the posterior circulation), which were determined by two radiologists and one neurosurgeon in consensus using CTA and digital subtraction angiography scans. CTA scans of the test set were then presented to three blinded radiologists (reader 1: 13, reader 2: 4, and reader 3: 3 years of experience in diagnostic neuroradiology), who assessed them individually for aneurysms. Detection sensitivities for aneurysms of the readers with and without the assistance of the DLM were compared. Results In the test set, the detection sensitivity of the DLM-Ens (85.7\%) was comparable to the radiologists (reader 1: 91.2\%, reader 2: 86.5\%, and reader 3: 86.5\%; Fleiss κ of 0.502). DLM-assistance significantly increased the detection sensitivity (reader 1: 97.6\%, reader 2: 97.6\%,and reader 3: 96.0\%; overall P=.024; Fleiss κ of 0.878), especially for secondary aneurysms (88.2\% of the additional aneurysms provided by the DLM). Conclusion Deep learning significantly improved the detection sensitivity of radiologists for aneurysms in aSAH, especially for secondary aneurysms. It therefore represents a valuable adjunct for physicians to establish an accurate diagnosis in order to optimize patient treatment.}, language = {en} } @article{PilgramEberweinWilleetal.2021, author = {Pilgram, Lisa and Eberwein, Lukas and Wille, Kai and Koehler, Felix C. and Stecher, Melanie and Rieg, Siegbert and Kielstein, Jan T. and Jakob, Carolin E. M. and R{\"u}thrich, Maria and Burst, Volker and Prasser, Fabian and Borgmann, Stefan and M{\"u}ller, Roman-Ulrich and Lanznaster, Julia and Isberner, Nora and Tometten, Lukas and Dolff, Sebastian}, title = {Clinical course and predictive risk factors for fatal outcome of SARS-CoV-2 infection in patients with chronic kidney disease}, series = {Infection}, volume = {49}, journal = {Infection}, number = {4}, organization = {LEOSS Study group}, issn = {0300-8126}, doi = {10.1007/s15010-021-01597-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308957}, pages = {725-737}, year = {2021}, abstract = {Purpose The ongoing pandemic caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has stressed health systems worldwide. Patients with chronic kidney disease (CKD) seem to be more prone to a severe course of coronavirus disease (COVID-19) due to comorbidities and an altered immune system. The study's aim was to identify factors predicting mortality among SARS-CoV-2-infected patients with CKD. Methods We analyzed 2817 SARS-CoV-2-infected patients enrolled in the Lean European Open Survey on SARS-CoV-2-infected patients and identified 426 patients with pre-existing CKD. Group comparisons were performed via Chi-squared test. Using univariate and multivariable logistic regression, predictive factors for mortality were identified. Results Comparative analyses to patients without CKD revealed a higher mortality (140/426, 32.9\% versus 354/2391, 14.8\%). Higher age could be confirmed as a demographic predictor for mortality in CKD patients (> 85 years compared to 15-65 years, adjusted odds ratio (aOR) 6.49, 95\% CI 1.27-33.20, p = 0.025). We further identified markedly elevated lactate dehydrogenase (> 2 × upper limit of normal, aOR 23.21, 95\% CI 3.66-147.11, p < 0.001), thrombocytopenia (< 120,000/µl, aOR 11.66, 95\% CI 2.49-54.70, p = 0.002), anemia (Hb < 10 g/dl, aOR 3.21, 95\% CI 1.17-8.82, p = 0.024), and C-reactive protein (≥ 30 mg/l, aOR 3.44, 95\% CI 1.13-10.45, p = 0.029) as predictors, while renal replacement therapy was not related to mortality (aOR 1.15, 95\% CI 0.68-1.93, p = 0.611). Conclusion The identified predictors include routinely measured and universally available parameters. Their assessment might facilitate risk stratification in this highly vulnerable cohort as early as at initial medical evaluation for SARS-CoV-2.}, language = {en} } @article{HornKristLiebetal.2021, author = {Horn, A. and Krist, L. and Lieb, W. and Montellano, F. A. and Kohls, M. and Haas, K. and Gelbrich, G. and Bolay-Gehrig, S. J. and Morbach, C. and Reese, J. P. and St{\"o}rk, S. and Fricke, J. and Zoller, T. and Schmidt, S. and Triller, P. and Kretzler, L. and R{\"o}nnefarth, M. and Von Kalle, C. and Willich, S. N. and Kurth, F. and Steinbeis, F. and Witzenrath, M. and Bahmer, T. and Hermes, A. and Krawczak, M. and Reinke, L. and Maetzler, C. and Franzenburg, J. and Enderle, J. and Flinspach, A. and Vehreschild, J. and Schons, M. and Illig, T. and Anton, G. and Ungeth{\"u}m, K. and Finkenberg, B. C. and Gehrig, M. T. and Savaskan, N. and Heuschmann, P. U. and Keil, T. and Schreiber, S.}, title = {Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP)}, series = {Infection}, volume = {49}, journal = {Infection}, number = {6}, issn = {0300-8126}, doi = {10.1007/s15010-021-01707-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308960}, pages = {1277-1287}, year = {2021}, abstract = {Purpose Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. Methods The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, W{\"u}rzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. Results As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36\% wished to participate and 1295 have already been examined at least once. Conclusion NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. Trial registration Registered at the German registry for clinical studies (DRKS00023742).}, language = {en} } @article{DichtlKocForsteretal.2021, author = {Dichtl, Karl and Koc, {\"O}zlem and Forster, Johannes and Scharf, Christina and Suerbaum, Sebastian and Andrassy, Joachim and Wagener, Johannes and Schroeder, Ines}, title = {An invasive infection caused by the thermophilic mold Talaromyces thermophilus}, series = {Infection}, volume = {49}, journal = {Infection}, number = {6}, issn = {0300-8126}, doi = {10.1007/s15010-021-01648-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308970}, pages = {1347-1353}, year = {2021}, abstract = {Background Increasing incidence of invasive infections caused by rare fungi was observed over the recent years. Case Here, we describe the first reported case of an infection caused by the thermophilic mold Talaromyces thermophilus. Cultivation and, hence, identification of this fastidious organism is challenging since standard incubation conditions are not sufficient. Retrospective analysis of patient samples and in vitro experiments demonstrated that testing for fungal antigens, i.e., the cell wall components galactomannan and β-1,3-D-glucan, is a promising tool.}, language = {en} } @article{JockelSchneiderSchlagenhaufPetsosetal.2021, author = {Jockel-Schneider, Yvonne and Schlagenhauf, Ulrich and Petsos, Hari and R{\"u}ttermann, Stefan and Schmidt, Jana and Ziebolz, Dirk and Wehner, Christian and Laky, Markus and Rott, Thea and Noack, Michael and Noack, Barbara and Lorenz, Katrin}, title = {Impact of 0.1\% octenidine mouthwash on plaque re-growth in healthy adults: a multi-center phase 3 randomized clinical trial}, series = {Clinical Oral Investigations}, volume = {25}, journal = {Clinical Oral Investigations}, number = {7}, issn = {1432-6981}, doi = {10.1007/s00784-021-03781-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307629}, pages = {4681-4689}, year = {2021}, abstract = {Objectives To investigate plaque inhibition of 0.1\% octenidine mouthwash (OCT) vs. placebo over 5 days in the absence of mechanical plaque control. Materials and methods For this randomized, placebo-controlled, double-blind, parallel group, multi-center phase 3 study, 201 healthy adults were recruited. After baseline recording of plaque index (PI) and gingival index (GI), collection of salivary samples, and dental prophylaxis, subjects were randomly assigned to OCT or placebo mouthwash in a 3:1 ratio. Rinsing was performed twice daily for 30 s. Colony forming units in saliva were determined before and after the first rinse. At day 5, PI, GI, and tooth discoloration index (DI) were assessed. Non-parametric van Elteren tests were applied with a significance level of p < 0.05. Results Treatment with OCT inhibited plaque formation more than treatment with placebo (PI: 0.36 vs. 1.29; p < 0.0001). OCT reduced GI (0.04 vs. placebo 0.00; p = 0.003) and salivary bacterial counts (2.73 vs. placebo 0.24 lgCFU/ml; p < 0.0001). Tooth discoloration was slightly higher under OCT (DI: 0.25 vs. placebo 0.00; p = 0.0011). Mild tongue staining and dysgeusia occurred. Conclusions OCT 0.1\% mouthwash inhibits plaque formation over 5 days. It therefore can be recommended when regular oral hygiene is temporarily compromised. Clinical relevance When individual plaque control is compromised, rinsing with octenidine mouthwash is recommended to maintain healthy oral conditions while side effects are limited.}, language = {en} }