@article{HeidrichWiegandBuggischetal.2014, author = {Heidrich, Benjamin and Wiegand, Steffen B. and Buggisch, Peter and Hinrichsen, Holger and Link, Ralph and M{\"o}ller, Bernd and B{\"o}ker, Klaus H. W. and Teuber, Gerlinde and Klinker, Hartwig and Zehnter, Elmar and Naumann, Uwe and Busch, Heiner W. and Maasoumy, Benjamin and Baum, Undine and Hardtke, Svenja and Manns, Michael P. and Wedemeyer, Heiner and Petersen, J{\"o}rg and Cornberg, Markus}, title = {Treatment of Naive Patients with Chronic Hepatitis C Genotypes 2 and 3 with Pegylated Interferon Alpha and Ribavirin in a Real World Setting: Relevance for the New Era of DAA}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {10}, issn = {1932-6203}, doi = {10.1371/journal.pone.0108751}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115149}, pages = {e108751}, year = {2014}, abstract = {Evidence based clinical guidelines are implemented to treat patients efficiently that include efficacy, tolerability but also health economic considerations. This is of particular relevance to the new direct acting antiviral agents that have revolutionized treatment of chronic hepatitis C. For hepatitis C genotypes 2/3 interferon free treatment is already available with sofosbuvir plus ribavirin. However, treatment with sofosbuvir-based regimens is 10-20 times more expensive compared to pegylated interferon alfa and ribavirin (PegIFN/RBV). It has to be discussed if PegIFN/RBV is still an option for easy to treat patients. We assessed the treatment of patients with chronic hepatitis C genotypes 2/3 with PegIFN/RBV in a real world setting according to the latest German guidelines. Overall, 1006 patients were recruited into a prospective patient registry with 959 having started treatment. The intention-to-treat analysis showed poor SVR (GT2 61\%, GT3 47\%) while patients with adherence had excellent SVR in the per protocol analysis (GT2 96\%, GT3 90\%). According to guidelines, 283 patients were candidates for shorter treatment duration, namely a treatment of 16 weeks (baseline HCV-RNA <800.000 IU/mL, no cirrhosis and RVR). However, 65\% of these easy to treat patients have been treated longer than recommended that resulted in higher costs but not higher SVR rates. In conclusion, treatment with PegIFN/RBV in a real world setting can be highly effective yet similar effective than PegIFN +/- sofosbuvir/RBV in well-selected naive G2/3 patients. Full adherence to guidelines could be further improved, because it would be important in the new era with DAA, especially to safe resources.}, language = {en} } @article{EckardtStasikKrameretal.2021, author = {Eckardt, Jan-Niklas and Stasik, Sebastian and Kramer, Michael and R{\"o}llig, Christoph and Kr{\"a}mer, Alwin and Scholl, Sebastian and Hochhaus, Andreas and Crysandt, Martina and Br{\"u}mmendorf, Tim H. and Naumann, Ralph and Steffen, Bj{\"o}rn and Kunzmann, Volker and Einsele, Hermann and Schaich, Markus and Burchert, Andreas and Neubauer, Andreas and Sch{\"a}fer-Eckart, Kerstin and Schliemann, Christoph and Krause, Stefan W. and Herbst, Regina and H{\"a}nel, Mathias and Frickhofen, Norbert and Noppeney, Richard and Kaiser, Ulrich and Baldus, Claudia D. and Kaufmann, Martin and R{\´a}cil, Zdenek and Platzbecker, Uwe and Berdel, Wolfgang E. and Mayer, Jiř{\´i} and Serve, Hubert and M{\"u}ller-Tidow, Carsten and Ehninger, Gerhard and St{\"o}lzel, Friedrich and Kroschinsky, Frank and Schetelig, Johannes and Bornh{\"a}user, Martin and Thiede, Christian and Middeke, Jan Moritz}, title = {Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {9}, issn = {2072-6694}, doi = {10.3390/cancers13092095}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236735}, year = {2021}, abstract = {Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6\%) and 53 patients (3.5\%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95\%-Confidence Interval (CI): 1.005-2.134), p = 0.047), relapse-free survival (HR = 1.904 (95\%-CI: 1.163-3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95\%-CI: 0.990-2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.}, language = {en} } @article{CornbergStoehrNaumannetal.2022, author = {Cornberg, Markus and Stoehr, Albrecht and Naumann, Uwe and Teuber, Gerlinde and Klinker, Hartwig and Lutz, Thomas and M{\"o}ller, Hj{\"o}rdis and Hidde, Dennis and Lohmann, Kristina and Simon, Karl-Georg}, title = {Real-world safety, effectiveness, and patient-reported outcomes in patients with chronic hepatitis C virus infection treated with glecaprevir/pibrentasvir: updated data from the German Hepatitis C-Registry (DHC-R)}, series = {Viruses}, volume = {14}, journal = {Viruses}, number = {7}, issn = {1999-4915}, doi = {10.3390/v14071541}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281939}, year = {2022}, abstract = {Using data from the German Hepatitis C-Registry (Deutsche Hepatitis C-Register, DHC-R), we report the real-world safety and effectiveness of glecaprevir/pibrentasvir (GLE/PIB) treatment and its impact on patient-reported outcomes (PROs) in underserved populations who are not typically included in clinical trials, yet who will be crucial for achieving hepatitis C virus (HCV) elimination. The DHC-R is an ongoing, non-interventional, multicenter, prospective, observational cohort study on patients treated for chronic HCV infection in Germany. The data cutoff was 17 January 2021. The primary effectiveness endpoint was sustained virologic response at post-treatment Week 12 (SVR12). Safety outcomes were assessed in all patients receiving GLE/PIB. PROs were assessed using the SF-36 survey. Of 2354 patients, 1964 had valid SVR12 data (intention-to-treat analysis). Of these, 1905 (97.0\%) achieved SVR12 with rates similar across the comorbidities analyzed, except for people who actively use drugs (PWUD (active)) (86.4\%). Excluding those who discontinued treatment and did not achieve SVR12, or were reinfected with HCV, the rate was 99.3\%, with similar results regardless of comorbidity. PWUD (active) and those with psychiatric disorders had the most meaningful improvements in PROs. Adverse events (AEs) occurred in 631/2354 patients (26.8\%), and serious AEs in 44 patients (1.9\%). GLE/PIB was highly effective and well tolerated in this real-world study of patient groups key to HCV elimination.}, language = {en} } @article{VollmuthMuljukovAbuMugheisibetal.2021, author = {Vollmuth, Christoph and Muljukov, Olga and Abu-Mugheisib, Mazen and Angermeier, Anselm and Barlinn, Jessica and Busetto, Loraine and Grau, Armin J. and G{\"u}nther, Albrecht and Gumbinger, Christoph and Hubert, Nikolai and H{\"u}ttemann, Katrin and Klingner, Carsten and Naumann, Markus and Palm, Frederick and Remi, Jan and R{\"u}cker, Viktoria and Schessl, Joachim and Schlachetzki, Felix and Schuppner, Ramona and Schwab, Stefan and Schwartz, Andreas and Trommer, Adrian and Urbanek, Christian and Volbers, Bastian and Weber, Joachim and Wojciechowski, Claudia and Worthmann, Hans and Zickler, Philipp and Heuschmann, Peter U. and Haeusler, Karl Georg and Hubert, Gordian Jan}, title = {Impact of the coronavirus disease 2019 pandemic on stroke teleconsultations in Germany in the first half of 2020}, series = {European Journal of Neurology}, volume = {28}, journal = {European Journal of Neurology}, number = {10}, doi = {10.1111/ene.14787}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259396}, pages = {3267-3278}, year = {2021}, abstract = {Background and purpose The effects of the coronavirus disease 2019 (COVID-19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany. Methods In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in-hospital and (telemedical) stroke care during the pandemic was conducted. Results Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID-19 measures in May/June 2020 were observed. Compared to 2018-2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3\% vs. 14.6\%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0\% vs. 22.1\%; p = 0.052). Despite the majority of participating network centers treating patients with COVID-19, there were no relevant shortcomings reported regarding in-hospital stroke treatment or telemedical stroke care. Conclusions Telemedical stroke care in Germany was able to provide full service despite the COVID-19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID-19 measures in Germany.}, 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} } @article{ElHelouBiegnerBodeetal.2019, author = {El-Helou, Sabine M. and Biegner, Anika-Kerstin and Bode, Sebastian and Ehl, Stephan R. and Heeg, Maximilian and Maccari, Maria E. and Ritterbusch, Henrike and Speckmann, Carsten and Rusch, Stephan and Scheible, Raphael and Warnatz, Klaus and Atschekzei, Faranaz and Beider, Renata and Ernst, Diana and Gerschmann, Stev and Jablonka, Alexandra and Mielke, Gudrun and Schmidt, Reinhold E. and Sch{\"u}rmann, Gesine and Sogkas, Georgios and Baumann, Ulrich H. and Klemann, Christian and Viemann, Dorothee and Bernuth, Horst von and Kr{\"u}ger, Renate and Hanitsch, Leif G. and Scheibenbogen, Carmen M. and Wittke, Kirsten and Albert, Michael H. and Eichinger, Anna and Hauck, Fabian and Klein, Christoph and Rack-Hoch, Anita and Sollinger, Franz M. and Avila, Anne and Borte, Michael and Borte, Stephan and Fasshauer, Maria and Hauenherm, Anja and Kellner, Nils and M{\"u}ller, Anna H. and {\"U}lzen, Anett and Bader, Peter and Bakhtiar, Shahrzad and Lee, Jae-Yun and Heß, Ursula and Schubert, Ralf and W{\"o}lke, Sandra and Zielen, Stefan and Ghosh, Sujal and Laws, Hans-Juergen and Neubert, Jennifer and Oommen, Prasad T. and H{\"o}nig, Manfred and Schulz, Ansgar and Steinmann, Sandra and Klaus, Schwarz and D{\"u}ckers, Gregor and Lamers, Beate and Langemeyer, Vanessa and Niehues, Tim and Shai, Sonu and Graf, Dagmar and M{\"u}glich, Carmen and Schmalzing, Marc T. and Schwaneck, Eva C. and Tony, Hans-Peter and Dirks, Johannes and Haase, Gabriele and Liese, Johannes G. and Morbach, Henner and Foell, Dirk and Hellige, Antje and Wittkowski, Helmut and Masjosthusmann, Katja and Mohr, Michael and Geberzahn, Linda and Hedrich, Christian M. and M{\"u}ller, Christiane and R{\"o}sen-Wolff, Angela and Roesler, Joachim and Zimmermann, Antje and Behrends, Uta and Rieber, Nikolaus and Schauer, Uwe and Handgretinger, Rupert and Holzer, Ursula and Henes, J{\"o}rg and Kanz, Lothar and Boesecke, Christoph and Rockstroh, J{\"u}rgen K. and Schwarze-Zander, Carolynne and Wasmuth, Jan-Christian and Dilloo, Dagmar and H{\"u}lsmann, Brigitte and Sch{\"o}nberger, Stefan and Schreiber, Stefan and Zeuner, Rainald and Ankermann, Tobias and Bismarck, Philipp von and Huppertz, Hans-Iko and Kaiser-Labusch, Petra and Greil, Johann and Jakoby, Donate and Kulozik, Andreas E. and Metzler, Markus and Naumann-Bartsch, Nora and Sobik, Bettina and Graf, Norbert and Heine, Sabine and Kobbe, Robin and Lehmberg, Kai and M{\"u}ller, Ingo and Herrmann, Friedrich and Horneff, Gerd and Klein, Ariane and Peitz, Joachim and Schmidt, Nadine and Bielack, Stefan and Groß-Wieltsch, Ute and Classen, Carl F. and Klasen, Jessica and Deutz, Peter and Kamitz, Dirk and Lassy, Lisa and Tenbrock, Klaus and Wagner, Norbert and Bernbeck, Benedikt and Brummel, Bastian and Lara-Villacanas, Eusebia and M{\"u}nstermann, Esther and Schneider, Dominik T. and Tietsch, Nadine and Westkemper, Marco and Weiß, Michael and Kramm, Christof and K{\"u}hnle, Ingrid and Kullmann, Silke and Girschick, Hermann and Specker, Christof and Vinnemeier-Laubenthal, Elisabeth and Haenicke, Henriette and Schulz, Claudia and Schweigerer, Lothar and M{\"u}ller, Thomas G. and Stiefel, Martina and Belohradsky, Bernd H. and Soetedjo, Veronika and Kindle, Gerhard and Grimbacher, Bodo}, title = {The German national registry of primary immunodeficiencies (2012-2017)}, series = {Frontiers in Immunology}, volume = {10}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2019.01272}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226629}, year = {2019}, abstract = {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.}, language = {en} }