TY - JOUR A1 - Manchia, Mirko A1 - Adli, Mazda A1 - Akula, Nirmala A1 - Arda, Raffaella A1 - Aubry, Jean-Michel A1 - Backlund, Lena A1 - Banzato, Claudio E. M. A1 - Baune, Bernhard T. A1 - Bellivier, Frank A1 - Bengesser, Susanne A1 - Biernacka, Joanna M. A1 - Brichant-Petitjean, Clara A1 - Bui, Elise A1 - Calkin, Cynthia V. A1 - Cheng, Andrew Tai Ann A1 - Chillotti, Caterina A1 - Cichon, Sven A1 - Clark, Scott A1 - Czerski, Piotr M. A1 - Dantas, Clarissa A1 - Del Zompo, Maria A1 - DePaulo, J. Raymond A1 - Detera-Wadleigh, Sevilla D. A1 - Etain, Bruno A1 - Falkai, Peter A1 - Frisén, Louise A1 - Frye, Mark A. A1 - Fullerton, Jan A1 - Gard, Sébastien A1 - Garnham, Julie A1 - Goes, Fernando S. A1 - Grof, Paul A1 - Gruber, Oliver A1 - Hashimoto, Ryota A1 - Hauser, Joanna A1 - Heilbronner, Urs A1 - Hoban, Rebecca A1 - Hou, Liping A1 - Jamain, Stéphane A1 - Kahn, Jean-Pierre A1 - Kassem, Layla A1 - Kato, Tadafumi A1 - Kelsoe, John R. A1 - Kittel-Schneider, Sarah A1 - Kliwicki, Sebastian A1 - Kuo, Po-Hsiu A1 - Kusumi, Ichiro A1 - Laje, Gonzalo A1 - Lavebratt, Catharina A1 - Leboyer, Marion A1 - Leckband, Susan G. A1 - López Jaramillo, Carlos A. A1 - Maj, Mario A1 - Malafosse, Alain A1 - Martinsson, Lina A1 - Masui, Takuya A1 - Mitchell, Philip B. A1 - Mondimore, Frank A1 - Monteleone, Palmiero A1 - Nallet, Audrey A1 - Neuner, Maria A1 - Novák, Tomás A1 - O'Donovan, Claire A1 - Ösby, Urban A1 - Ozaki, Norio A1 - Perlis, Roy H. A1 - Pfennig, Andrea A1 - Potash, James B. A1 - Reich-Erkelenz, Daniela A1 - Reif, Andreas A1 - Reininghaus, Eva A1 - Richardson, Sara A1 - Rouleau, Guy A. A1 - Rybakowski, Janusz K. A1 - Schalling, Martin A1 - Schofield, Peter R. A1 - Schubert, Oliver K. A1 - Schweizer, Barbara A1 - Seemüller, Florian A1 - Grigoroiu-Serbanescu, Maria A1 - Severino, Giovanni A1 - Seymour, Lisa R. A1 - Slaney, Claire A1 - Smoller, Jordan W. A1 - Squassina, Alessio A1 - Stamm, Thomas A1 - Steele, Jo A1 - Stopkova, Pavla A1 - Tighe, Sarah K. A1 - Tortorella, Alfonso A1 - Turecki, Gustavo A1 - Wray, Naomi R. A1 - Wright, Adam A1 - Zandi, Peter P. A1 - Zilles, David A1 - Bauer, Michael A1 - Rietschel, Marcella A1 - McMahon, Francis J. A1 - Schulze, Thomas G. A1 - Alda, Martin T1 - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report JF - PLoS ONE N2 - Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. KW - age KW - observer agreement KW - prophylactic lithium KW - mapping susceptibility genes KW - mood disorders KW - onset KW - association KW - reliability KW - morality KW - illness Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130938 VL - 8 IS - 6 ER - TY - JOUR A1 - Hebestreit, Helge A1 - Zeidler, Cornelia A1 - Schippers, Christopher A1 - de Zwaan, Martina A1 - Deckert, Jürgen A1 - Heuschmann, Peter A1 - Krauth, Christian A1 - Bullinger, Monika A1 - Berger, Alexandra A1 - Berneburg, Mark A1 - Brandstetter, Lilly A1 - Deibele, Anna A1 - Dieris-Hirche, Jan A1 - Graessner, Holm A1 - Gündel, Harald A1 - Herpertz, Stephan A1 - Heuft, Gereon A1 - Lapstich, Anne-Marie A1 - Lücke, Thomas A1 - Maisch, Tim A1 - Mundlos, Christine A1 - Petermann-Meyer, Andrea A1 - Müller, Susanne A1 - Ott, Stephan A1 - Pfister, Lisa A1 - Quitmann, Julia A1 - Romanos, Marcel A1 - Rutsch, Frank A1 - Schaubert, Kristina A1 - Schubert, Katharina A1 - Schulz, Jörg B. A1 - Schweiger, Susann A1 - Tüscher, Oliver A1 - Ungethüm, Kathrin A1 - Wagner, Thomas O. F. A1 - Haas, Kirsten T1 - Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study JF - Orphanet Journal of Rare Diseases N2 - Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. KW - rare diseases KW - multi‑center cohort study KW - dual guidance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300440 VL - 17 IS - 1 ER - TY - JOUR A1 - Atanasov, Georgi A1 - Benkert, Christoph A1 - Thelen, Armin A1 - Tappe, Dennis A1 - Frosch, Matthias A1 - Teichmann, Dieter A1 - Barth, Thomas F. E. A1 - Wittekind, Christian A1 - Schubert, Stefan A1 - Jonas, Sven T1 - Alveolar echinococcosis-spreading disease challenging clinicians: A case report and literature review JF - World Journal of Gastroenterology N2 - Human alveolar echinococcosis (AE) is a potentially deadly disease; recent studies have shown that the endemic area of Echinococcus multilocularis, its causative agent, is larger than previously known. This disease has low prevalence and remains underreported in Europe. Emerging clinical data show that diagnostic difficulties are still common. We report on a 76-year old patient suffering from AE lesions restricted to the left lobe of the liver who underwent a curative extended left hemihepatectomy. Prior to the resection a liver biopsy under the suspicion of an atypical malignancy was performed. After the intervention he developed a pseudoaneurysm of the hepatic artery that was successfully coiled. Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a gross tumour composed of multiple large vesicles with several centimeters in diameter. In addition, there were neither extensive adhesions nor infiltrations of the neighboring pancreas and diaphragm as was expected from previous imaging results. The unexpected diagnosis of AE was confirmed by definite histopathology, specific polymerase chain reaction and serology results. This is a rare case of unusual macroscopic presentation of AE that posed immense diagnostic challenges and had an eventful course. To our knowledge this is the first case of an autochthonous infection in this particular geographic area of Germany, the federal state of Saxony. This report may provide new hints for an expanding area of risk for AE and emphasizes the risk of complications in the scope of diagnostic procedures and the limitations of modern radiological imaging. KW - hemihepatectomy KW - multilocularis KW - Germany KW - Europe KW - liver KW - alveolar echinococcosis KW - echinococcus multilocularis KW - autochthonous infection KW - liver resection Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131525 VL - 19 IS - 26 ER - TY - JOUR A1 - Staab, Torsten E. M. A1 - Lotter, Frank A1 - Mühle, Uwe A1 - Elsayed, Mohamed A1 - Petschke, Danny A1 - Schubert, Thomas A1 - Ibrahim, Alaa M. A1 - Krause-Rehberg, Reinhard A1 - Kieback, Bernd T1 - The decomposition process in high-purity Al-1.7 at.% Cu alloys with trace elements: preservation of quenched-in vacancies by In, Sn and Pb influencing the ​θ′formation JF - Journal of Materials Science N2 - Aluminium-copper alloys of the 2xxx type receive their excellent mechanical properties by the formation of copper-rich precipitates during hardening. Size, distribution and crystal structure of the formed precipitates determine the final strength of those alloys. Adding traces of certain elements, which bind to vacancies, significantly influences the decomposition behaviour, i.e. the diffusion of the copper atoms. For high-purity ternary alloys (Al-1.7 at.% Cu-X), we investigate the interaction of copper and trace element atoms (X=In, Sn, and Pb) with quenched-in vacancies by Positron Annihilation Lifetime Spectroscopy (PALS). By employing Vickers microhardness, Differential Scanning Calorimetry (DSC) and Small Angle X-Ray Scattering (SAXS) we obtain a comprehensive picture of the decomposition process: opposite to predicted binding energies to vacancies by ab-initio calculations we find during ageing at room and elevated temperature a more retarded clustering of copper in the presence of In rather than for Sn additions, while Pb, having the highest predicted binding to vacancies, shows nearly no retarding effect compared to pure Al-Cu. If the latter would be due to a limited solubility of lead, it had to be below 2 ppm. Transmission Electron Microscopy (TEM) as imaging method complements our findings. Annealing the quenched Al-1.7 at.% Cu-X-alloys containing 100 ppm In or Sn at 150∘C leads to finely distributed θ′-precipitates on the nanoscale, since due to the trace additions the formation temperature of θ′ is lowered by more than 100∘C. According to TEM small agglomerates of trace elements (In, Sn) may support the early nucleation for the θ′-precipitates. KW - Aluminium-copper KW - alloys KW - trace elements Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-269103 SN - 1573-4803 VL - 56 IS - 14 ER - TY - JOUR A1 - Peters, Simon A1 - Fohmann, Ingo A1 - Rudel, Thomas A1 - Schubert-Unkmeir, Alexandra T1 - A Comprehensive Review on the Interplay between Neisseria spp. and Host Sphingolipid Metabolites JF - Cells N2 - Sphingolipids represent a class of structural related lipids involved in membrane biology and various cellular processes including cell growth, apoptosis, inflammation and migration. Over the past decade, sphingolipids have become the focus of intensive studies regarding their involvement in infectious diseases. Pathogens can manipulate the sphingolipid metabolism resulting in cell membrane reorganization and receptor recruitment to facilitate their entry. They may recruit specific host sphingolipid metabolites to establish a favorable niche for intracellular survival and proliferation. In contrast, some sphingolipid metabolites can also act as a first line defense against bacteria based on their antimicrobial activity. In this review, we will focus on the strategies employed by pathogenic Neisseria spp. to modulate the sphingolipid metabolism and hijack the sphingolipid balance in the host to promote cellular colonization, invasion and intracellular survival. Novel techniques and innovative approaches will be highlighted that allow imaging of sphingolipid derivatives in the host cell as well as in the pathogen. KW - sphingolipids KW - host–pathogen interaction KW - Neisseria meningitidis KW - Neisseria gonorrhoeae Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250203 SN - 2073-4409 VL - 10 IS - 11 ER - TY - JOUR A1 - El-Helou, Sabine M. A1 - Biegner, Anika-Kerstin A1 - Bode, Sebastian A1 - Ehl, Stephan R. A1 - Heeg, Maximilian A1 - Maccari, Maria E. A1 - Ritterbusch, Henrike A1 - Speckmann, Carsten A1 - Rusch, Stephan A1 - Scheible, Raphael A1 - Warnatz, Klaus A1 - Atschekzei, Faranaz A1 - Beider, Renata A1 - Ernst, Diana A1 - Gerschmann, Stev A1 - Jablonka, Alexandra A1 - Mielke, Gudrun A1 - Schmidt, Reinhold E. A1 - Schürmann, Gesine A1 - Sogkas, Georgios A1 - Baumann, Ulrich H. A1 - Klemann, Christian A1 - Viemann, Dorothee A1 - Bernuth, Horst von A1 - Krüger, Renate A1 - Hanitsch, Leif G. A1 - Scheibenbogen, Carmen M. A1 - Wittke, Kirsten A1 - Albert, Michael H. A1 - Eichinger, Anna A1 - Hauck, Fabian A1 - Klein, Christoph A1 - Rack-Hoch, Anita A1 - Sollinger, Franz M. A1 - Avila, Anne A1 - Borte, Michael A1 - Borte, Stephan A1 - Fasshauer, Maria A1 - Hauenherm, Anja A1 - Kellner, Nils A1 - Müller, Anna H. A1 - Ülzen, Anett A1 - Bader, Peter A1 - Bakhtiar, Shahrzad A1 - Lee, Jae-Yun A1 - Heß, Ursula A1 - Schubert, Ralf A1 - Wölke, Sandra A1 - Zielen, Stefan A1 - Ghosh, Sujal A1 - Laws, Hans-Juergen A1 - Neubert, Jennifer A1 - Oommen, Prasad T. A1 - Hönig, Manfred A1 - Schulz, Ansgar A1 - Steinmann, Sandra A1 - Klaus, Schwarz A1 - Dückers, Gregor A1 - Lamers, Beate A1 - Langemeyer, Vanessa A1 - Niehues, Tim A1 - Shai, Sonu A1 - Graf, Dagmar A1 - Müglich, Carmen A1 - Schmalzing, Marc T. A1 - Schwaneck, Eva C. A1 - Tony, Hans-Peter A1 - Dirks, Johannes A1 - Haase, Gabriele A1 - Liese, Johannes G. A1 - Morbach, Henner A1 - Foell, Dirk A1 - Hellige, Antje A1 - Wittkowski, Helmut A1 - Masjosthusmann, Katja A1 - Mohr, Michael A1 - Geberzahn, Linda A1 - Hedrich, Christian M. A1 - Müller, Christiane A1 - Rösen-Wolff, Angela A1 - Roesler, Joachim A1 - Zimmermann, Antje A1 - Behrends, Uta A1 - Rieber, Nikolaus A1 - Schauer, Uwe A1 - Handgretinger, Rupert A1 - Holzer, Ursula A1 - Henes, Jörg A1 - Kanz, Lothar A1 - Boesecke, Christoph A1 - Rockstroh, Jürgen K. A1 - Schwarze-Zander, Carolynne A1 - Wasmuth, Jan-Christian A1 - Dilloo, Dagmar A1 - Hülsmann, Brigitte A1 - Schönberger, Stefan A1 - Schreiber, Stefan A1 - Zeuner, Rainald A1 - Ankermann, Tobias A1 - Bismarck, Philipp von A1 - Huppertz, Hans-Iko A1 - Kaiser-Labusch, Petra A1 - Greil, Johann A1 - Jakoby, Donate A1 - Kulozik, Andreas E. A1 - Metzler, Markus A1 - Naumann-Bartsch, Nora A1 - Sobik, Bettina A1 - Graf, Norbert A1 - Heine, Sabine A1 - Kobbe, Robin A1 - Lehmberg, Kai A1 - Müller, Ingo A1 - Herrmann, Friedrich A1 - Horneff, Gerd A1 - Klein, Ariane A1 - Peitz, Joachim A1 - Schmidt, Nadine A1 - Bielack, Stefan A1 - Groß-Wieltsch, Ute A1 - Classen, Carl F. A1 - Klasen, Jessica A1 - Deutz, Peter A1 - Kamitz, Dirk A1 - Lassy, Lisa A1 - Tenbrock, Klaus A1 - Wagner, Norbert A1 - Bernbeck, Benedikt A1 - Brummel, Bastian A1 - Lara-Villacanas, Eusebia A1 - Münstermann, Esther A1 - Schneider, Dominik T. A1 - Tietsch, Nadine A1 - Westkemper, Marco A1 - Weiß, Michael A1 - Kramm, Christof A1 - Kühnle, Ingrid A1 - Kullmann, Silke A1 - Girschick, Hermann A1 - Specker, Christof A1 - Vinnemeier-Laubenthal, Elisabeth A1 - Haenicke, Henriette A1 - Schulz, Claudia A1 - Schweigerer, Lothar A1 - Müller, Thomas G. A1 - Stiefel, Martina A1 - Belohradsky, Bernd H. A1 - Soetedjo, Veronika A1 - Kindle, Gerhard A1 - Grimbacher, Bodo T1 - The German national registry of primary immunodeficiencies (2012-2017) JF - Frontiers in Immunology N2 - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment. KW - registry for primary immunodeficiency KW - primary immunodeficiency (PID) KW - German PID-NET registry KW - PID prevalence KW - European Society for Immunodeficiencies (ESID) KW - IgG substitution therapy KW - CVID Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629 VL - 10 ER -