@article{WildeLiebLeichtetal.2021, author = {Wilde, Anne-Christin Beatrice and Lieb, Charlotte and Leicht, Elise and Greverath, Lena Maria and Steinhagen, Lara Marleen and Wald de Chamorro, Nina and Petersen, J{\"o}rg and Hofmann, Wolf Peter and Hinrichsen, Holger and Heyne, Renate and Berg, Thomas and Naumann, Uwe and Schwenzer, Jeannette and Vermehren, Johannes and Geier, Andreas and Tacke, Frank and M{\"u}ller, Tobias}, title = {Real-world clinical management of patients with primary biliary cholangitis — a retrospective multicenter study from Germany}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, number = {5}, issn = {2077-0383}, doi = {10.3390/jcm10051061}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234003}, year = {2021}, abstract = {Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3\% of patients, respectively. In 83.8\% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2\%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60\%, p = 0.005), Barcelona (13 vs. 34\%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75\%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74\%, p = 0.004; Barcelona: 50 vs. 84\%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86\%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.}, language = {en} } @article{RauSchmittBergetal.2018, author = {Rau, Monika and Schmitt, Johannes and Berg, Thomas and Kremer, Andreas E. and Stieger, Bruno and Spanaus, Katharina and Bengsch, Bertram and Romero, Marta R. and Marin, Jose J. and Keitel, Verena and Klinker, Hartwig and Tony, Hans-Peter and M{\"u}llhaupt, Beat and Geier, Andreas}, title = {Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0208225}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177674}, pages = {e0208225}, year = {2018}, abstract = {Background \& aims Serum interferon-gamma-inducible protein-10 (IP-10) is elevated in cholestatic liver diseases and predicts response to antiviral therapy in patients with chronic hepatitis C virus (HCV) infection. Dipeptidylpeptidase 4 (DPPIV) cleaves active IP-10 into an inactive form, which inhibits recruitment of CXCR3+ T cells to the liver. In this study the link between IP-10 levels, DPPIV activity in serum and CXCR3+ T cells is analysed in cholestatic and non-cholestatic liver patients. Methods In serum DPPIV activity (by enzymatic assay), IP-10 (by ELISA) and bile acids (BA) (by enzymatic assay) were analysed in 229 naive HCV genotype (GT) 1 patients and in 16 patients with cholestatic liver disease. In a prospective follow-up (FU) cohort of 27 HCV GT 1 patients peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ cells were measured by FACS. Results In 229 HCV patients serum IP-10 levels correlated positively to DPPIV serum activity. Higher IP-10 levels and DPPIV activity were detected in cholestatic and in cirrhotic HCV patients. Increased IP-10 serum levels were associated with therapeutic non-response to antiviral treatment with pegylated-interferon and ribavirin. In the HCV FU cohort elevated IP-10 serum levels and increased BA were associated with higher frequencies of peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ T cells. Positive correlation between serum IP-10 levels and DPPIV activity was likewise validated in patients with cholestatic liver diseases. Conclusions A strong correlation between elevated serum levels of IP-10 and DPPIV activity was seen in different cholestatic patient groups. Furthermore, in cholestatic HCV patients a functional link to increased numbers of peripheral CXCR3+ immune cells could be observed. The source of DPPIV release in cholestatic patients remains open.}, language = {en} } @article{MuellerGirardHopfneretal.2016, author = {M{\"u}ller, Stefanie H. and Girard, Simon L. and Hopfner, Franziska and Merner, Nancy D. and Bourassa, Cynthia V. and Lorenz, Delia and Clark, Lorraine N. and Tittmann, Lukas and Soto-Ortolaza, Alexandra I. and Klebe, Stephan and Hallett, Mark and Schneider, Susanne A. and Hodgkinson, Colin A. and Lieb, Wolfgang and Wszolek, Zbigniew K. and Pendziwiat, Manuela and Lorenzo-Betancor, Oswaldo and Poewe, Werner and Ortega-Cubero, Sara and Seppi, Klaus and Rajput, Alex and Hussl, Anna and Rajput, Ali H. and Berg, Daniela and Dion, Patrick A. and Wurster, Isabel and Shulman, Joshua M. and Srulijes, Karin and Haubenberger, Dietrich and Pastor, Pau and Vilari{\~n}o-G{\"u}ell, Carles and Postuma, Ronald B. and Bernard, Genevi{\`e}ve and Ladwig, Karl-Heinz and Dupr{\´e}, Nicolas and Jankovic, Joseph and Strauch, Konstantin and Panisset, Michel and Winkelmann, Juliane and Testa, Claudia M. and Reischl, Eva and Zeuner, Kirsten E. and Ross, Owen A. and Arzberger, Thomas and Chouinard, Sylvain and Deuschl, G{\"u}nther and Louis, Elan D. and Kuhlenb{\"a}umer, Gregor and Rouleau, Guy A.}, title = {Genome-wide association study in essential tremor identifies three new loci}, series = {Brain}, volume = {139}, journal = {Brain}, doi = {10.1093/brain/aww242}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186541}, pages = {3163-3169}, year = {2016}, abstract = {We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.}, language = {en} } @article{MorisChristmannWirtgenetal.2021, author = {Moris, Victoria C. and Christmann, Katharina and Wirtgen, Aline and Belokobylskij, Sergey A. and Berg, Alexander and Liebig, Wolf-Harald and Soon, Villu and Baur, Hannes and Schmitt, Thomas and Niehuis, Oliver}, title = {Cuticular hydrocarbons on old museum specimens of the spiny mason wasp, Odynerus spinipes (Hymenoptera: Vespidae: Eumeninae), shed light on the distribution and on regional frequencies of distinct chemotypes}, series = {Chemoecology}, volume = {31}, journal = {Chemoecology}, number = {5}, issn = {0937-7409}, doi = {10.1007/s00049-021-00350-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-306999}, pages = {311-322}, year = {2021}, abstract = {The mason wasp Odynerus spinipes shows an exceptional case of intrasexual cuticular hydrocarbon (CHC) profile dimorphism. Females of this species display one of two CHC profiles (chemotypes) that differ qualitatively and quantitatively from each other. The ratio of the two chemotypes was previously shown to be close to 1:1 at three sites in Southern Germany, which might not be representative given the Palearctic distribution of the species. To infer the frequency of the two chemotypes across the entire distributional range of the species, we analyzed with GC-MS the CHC profile of 1042 dry-mounted specimens stored in private and museum collections. We complemented our sampling by including 324 samples collected and preserved specifically for studying their CHCs. We were capable of reliably identifying the chemotypes in 91\% of dry-mounted samples, some of which collected almost 200 years ago. We found both chemotypes to occur in the Far East, the presumed glacial refuge of the species, and their frequency to differ considerably between sites and geographic regions. The geographic structure in the chemotype frequencies could be the result of differential selection regimes and/or different dispersal routes during the colonization of the Western Palearctic. The presented data pave the route for disentangling these factors by providing information where to geographically sample O. spinipes for population genetic analyses. They also form the much-needed basis for future studies aiming to understand the evolutionary and geographic origin as well as the genetics of the astounding CHC profile dimorphism that O. spinipes females exhibit.}, language = {en} } @article{KoehlerAdamFussetal.2022, author = {Koehler, Viktoria Florentine and Adam, Pia and Fuss, Carmina Teresa and Jiang, Linmiao and Berg, Elke and Frank-Raue, Karin and Raue, Friedhelm and Hoster, Eva and Kn{\"o}sel, Thomas and Schildhaus, Hans-Ulrich and Negele, Thomas and Siebolts, Udo and Lorenz, Kerstin and Allelein, Stephanie and Schott, Matthias and Spitzweg, Christine and Kroiss, Matthias}, title = {Treatment of RET-positive advanced medullary thyroid cancer with multi-tyrosine kinase inhibitors — a retrospective multi-center registry analysis}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {14}, issn = {2072-6694}, doi = {10.3390/cancers14143405}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281776}, year = {2022}, abstract = {Background: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual outcome of patients with RET-positive MTC treated with MKIs is ill described. Methods: We here retrospectively determined the RET oncogene variant status with a targeted DNA Custom Panel in a prospectively collected cohort of 48 patients with advanced MTC treated with vandetanib and/or cabozantinib at four German referral centers. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. Results: In total, 44/48 (92\%) patients had germline or somatic RET variants. The M918T variant was found in 29/44 (66\%) cases. In total, 2/32 (6\%) patients with a somatic RET variant had further somatic variants, while in 1/32 (3\%) patient with a germline RET variant, additional variants were found. Only 1/48 (2\%) patient had a pathogenic HRAS variant, and no variants were found in 3 cases. In first-line treatment, the median OS was 53 (95\% CI (95\% confidence interval), 32-NR (not reached); n = 36), and the median PFS was 21 months (12-39; n = 33) in RET-positive MTC patients. In second-line treatment, the median OS was 18 (13-79; n = 22), and the median PFS was 3.5 months (2-14; n = 22) in RET-positive cases. Conclusions: RET variants were highly prevalent in patients with advanced MTC. The treatment results in RET-positive cases were similar to those reported in unselected cohorts.}, language = {en} } @article{HudsonNewboldContuetal.2014, author = {Hudson, Lawrence N. and Newbold, Tim and Contu, Sara and Hill, Samantha L. L. and Lysenko, Igor and De Palma, Adriana and Phillips, Helen R. P. and Senior, Rebecca A. and Bennett, Dominic J. and Booth, Hollie and Choimes, Argyrios and Correia, David L. P. and Day, Julie and Echeverria-Londono, Susy and Garon, Morgan and Harrison, Michelle L. K. and Ingram, Daniel J. and Jung, Martin and Kemp, Victoria and Kirkpatrick, Lucinda and Martin, Callum D. and Pan, Yuan and White, Hannah J. and Aben, Job and Abrahamczyk, Stefan and Adum, Gilbert B. and Aguilar-Barquero, Virginia and Aizen, Marcelo and Ancrenaz, Marc and Arbelaez-Cortes, Enrique and Armbrecht, Inge and Azhar, Badrul and Azpiroz, Adrian B. and Baeten, Lander and B{\´a}ldi, Andr{\´a}s and Banks, John E. and Barlow, Jos and Bat{\´a}ry, P{\´e}ter and Bates, Adam J. and Bayne, Erin M. and Beja, Pedro and Berg, Ake and Berry, Nicholas J. and Bicknell, Jake E. and Bihn, Jochen H. and B{\"o}hning-Gaese, Katrin and Boekhout, Teun and Boutin, Celine and Bouyer, Jeremy and Brearley, Francis Q. and Brito, Isabel and Brunet, J{\"o}rg and Buczkowski, Grzegorz and Buscardo, Erika and Cabra-Garcia, Jimmy and Calvino-Cancela, Maria and Cameron, Sydney A. and Cancello, Eliana M. and Carrijo, Tiago F. and Carvalho, Anelena L. and Castro, Helena and Castro-Luna, Alejandro A. and Cerda, Rolando and Cerezo, Alexis and Chauvat, Matthieu and Clarke, Frank M. and Cleary, Daniel F. R. and Connop, Stuart P. and D'Aniello, Biagio and da Silva, Pedro Giovani and Darvill, Ben and Dauber, Jens and Dejean, Alain and Diek{\"o}tter, Tim and Dominguez-Haydar, Yamileth and Dormann, Carsten F. and Dumont, Bertrand and Dures, Simon G. and Dynesius, Mats and Edenius, Lars and Elek, Zolt{\´a}n and Entling, Martin H. and Farwig, Nina and Fayle, Tom M. and Felicioli, Antonio and Felton, Annika M. and Ficetola, Gentile F. and Filgueiras, Bruno K. C. and Fonte, Steve J. and Fraser, Lauchlan H. and Fukuda, Daisuke and Furlani, Dario and Ganzhorn, J{\"o}rg U. and Garden, Jenni G. and Gheler-Costa, Carla and Giordani, Paolo and Giordano, Simonetta and Gottschalk, Marco S. and Goulson, Dave and Gove, Aaron D. and Grogan, James and Hanley, Mick E. and Hanson, Thor and Hashim, Nor R. and Hawes, Joseph E. and H{\´e}bert, Christian and Helden, Alvin J. and Henden, John-Andr{\´e} and Hern{\´a}ndez, Lionel and Herzog, Felix and Higuera-Diaz, Diego and Hilje, Branko and Horgan, Finbarr G. and Horv{\´a}th, Roland and Hylander, Kristoffer and Horv{\´a}th, Roland and Isaacs-Cubides, Paola and Ishitani, Mashiro and Jacobs, Carmen T. and Jaramillo, Victor J. and Jauker, Birgit and Jonsell, Matts and Jung, Thomas S. and Kapoor, Vena and Kati, Vassiliki and Katovai, Eric and Kessler, Michael and Knop, Eva and Kolb, Annette and K{\"o}r{\"o}si, {\`A}d{\´a}m and Lachat, Thibault and Lantschner, Victoria and Le F{\´e}on, Violette and LeBuhn, Gretchen and L{\´e}gar{\´e}, Jean-Philippe and Letcher, Susan G. and Littlewood, Nick A. and L{\´o}pez-Quintero, Carlos A. and Louhaichi, Mounir and L{\"o}vei, Gabor L. and Lucas-Borja, Manuel Esteban and Luja, Victor H. and Maeto, Kaoru and Magura, Tibor and Mallari, Neil Aldrin and Marin-Spiotta, Erika and Marhall, E. J. P. and Mart{\´i}nez, Eliana and Mayfield, Margaret M. and Mikusinski, Gregorz and Milder, Jeffery C. and Miller, James R. and Morales, Carolina L. and Muchane, Mary N. and Muchane, Muchai and Naidoo, Robin and Nakamura, Akihiro and Naoe, Shoji and Nates-Parra, Guiomar and Navarerete Gutierrez, Dario A. and Neuschulz, Eike L. and Noreika, Norbertas and Norfolk, Olivia and Noriega, Jorge Ari and N{\"o}ske, Nicole M. and O'Dea, Niall and Oduro, William and Ofori-Boateng, Caleb and Oke, Chris O. and Osgathorpe, Lynne M. and Paritsis, Juan and Parrah, Alejandro and Pelegrin, Nicol{\´a}s and Peres, Carlos A. and Persson, Anna S. and Petanidou, Theodora and Phalan, Ben and Philips, T. Keith and Poveda, Katja and Power, Eileen F. and Presley, Steven J. and Proen{\c{c}}a, V{\^a}nia and Quaranta, Marino and Quintero, Carolina and Redpath-Downing, Nicola A. and Reid, J. Leighton and Reis, Yana T. and Ribeiro, Danilo B. and Richardson, Barbara A. and Richardson, Michael J. and Robles, Carolina A. and R{\"o}mbke, J{\"o}rg and Romero-Duque, Luz Piedad and Rosselli, Loreta and Rossiter, Stephen J. and Roulston, T'ai H. and Rousseau, Laurent and Sadler, Jonathan P. and S{\´a}fi{\´a}n, Szbolcs and Salda{\~n}a-V{\´a}squez, Romeo A. and Samneg{\aa}rd, Ulrika and Sch{\"u}epp, Christof and Schweiger, Oliver and Sedlock, Jodi L. and Shahabuddin, Ghazala and Sheil, Douglas and Silva, Fernando A. B. and Slade, Eleanor and Smith-Pardo, Allan H. and Sodhi, Navjot S. and Somarriba, Eduardo J. and Sosa, Ram{\´o}n A. and Stout, Jane C. and Struebig, Matthew J. and Sung, Yik-Hei and Threlfall, Caragh G. and Tonietto, Rebecca and T{\´o}thm{\´e}r{\´e}sz, B{\´e}la and Tscharntke, Teja and Turner, Edgar C. and Tylianakis, Jason M. and Vanbergen, Adam J. and Vassilev, Kiril and Verboven, Hans A. F. and Vergara, Carlos H. and Vergara, Pablo M. and Verhulst, Jort and Walker, Tony R. and Wang, Yanping and Watling, James I. and Wells, Konstans and Williams, Christopher D. and Willig, Michael R. and Woinarski, John C. Z. and Wolf, Jan H. D. and Woodcock, Ben A. and Yu, Douglas W. and Zailsev, Andreys and Collen, Ben and Ewers, Rob M. and Mace, Georgina M. and Purves, Drew W. and Scharlemann, J{\"o}rn P. W. and Pervis, Andy}, title = {The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts}, series = {Ecology and Evolution}, volume = {4}, journal = {Ecology and Evolution}, number = {24}, doi = {10.1002/ece3.1303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114425}, pages = {4701 - 4735}, year = {2014}, abstract = {Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1\% of the total number of all species described, and more than 1\% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.}, language = {en} } @article{GrammatikosLangeSusseretal.2014, author = {Grammatikos, Georgios and Lange, Christian and Susser, Simon and Schwendy, Susanne and Dikopoulos, Nektarios and Buggisch, Peter and Encke, Jens and Teuber, Gerlinde and Goeser, Tobias and Thimme, Robert and Klinker, Hartwig and Boecher, Wulf O. and Schulte-Frohlinde, Ewert and Penna-Martinez, Marissa and Badenhoop, Klaus and Zeuzem, Stefan and Berg, Thomas and Sarrazin, Christoph}, title = {Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {2}, issn = {1932-6203}, doi = {10.1371/journal.pone.0087974}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117310}, pages = {e87974}, year = {2014}, abstract = {Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed. Methods: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-alpha and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. Results: Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) \% of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002-1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975-0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000-1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073-2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271-4.695, P = 0.007) constituted the strongest predictors of treatment response. Conclusions: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.}, language = {en} } @article{GrafMondorfKnopetal.2019, author = {Graf, Christiana and Mondorf, Antonia and Knop, Viola and Peiffer, Kai-Henrik and Dietz, Julia and Friess, Julia and Wedemeyer, Heiner and Buggisch, Peter and Mauss, Stefan and Berg, Thomas and Rausch, Michael and Sprinzl, Martin and Klinker, Hartwig and Hinrichsen, Holger and Bronowicki, Jean-Pierre and Haag, Sebastian and H{\"u}ppe, Dietrich and Lutz, Thomas and Poynard, Thierry and Zeuzem, Stefan and Friedrich-Rust, Mireen and Sarrazin, Christoph and Vermehren, Johannes}, title = {Evaluation of point shear wave elastography using acoustic radiation force impulse imaging for longitudinal fibrosis assessment in patients with HBeAg-Negative HBV infection}, series = {Journal of Clinical Medicine}, volume = {8}, journal = {Journal of Clinical Medicine}, number = {12}, issn = {2077-0383}, doi = {10.3390/jcm8122101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193916}, year = {2019}, abstract = {Background: Accurate assessment of hepatic fibrosis in patients with chronic HBeAg-negative Hepatitis B is of crucial importance not only to predict the long-term clinical course, but also to evaluate antiviral therapy indication. The aim of this study was to prospectively assess the utility of point shear wave elastography (pSWE) for longitudinal non-invasive fibrosis assessment in a large cohort of untreated patients with chronic HBeAg-negative hepatitis B virus (HBV) infection. Methods: 407 consecutive patients with HBeAg-negative HBV infection who underwent pSWE, transient elastography (TE) as well as laboratory fibrosis markers, including fibrosis index based on four factors (FIB-4), aspartate to platelet ratio index (APRI) and FibroTest, on the same day were prospectively followed up for six years. Patients were classified into one of the three groups: inactive carriers (IC; HBV-DNA <2000 IU/mL and ALT <40 U/L); grey zone group 1 (GZ-1; HBV DNA <2000 IU/mL and ALT >40 U/L); grey zone group 2 (GZ-2; HBV-DNA >2000 IU/mL and ALT <40 U/L). Results: pSWE results were significantly correlated with TE (r = 0.29, p < 0.001) and APRI (r = 0.17; p = 0.005). Median pSWE values did not differ between IC, GZ-1 and GZ-2 patients (p = 0.82, p = 0.17, p = 0.34). During six years of follow-up, median pSWE and TE values did not differ significantly over time (TE: p = 0.27; pSWE: p = 0.05). Conclusion: Our data indicate that pSWE could be useful for non-invasive fibrosis assessment and follow-up in patients with HBeAg-negative chronic HBV infection.}, language = {en} } @article{AdamKircherSbieraetal.2021, author = {Adam, Pia and Kircher, Stefan and Sbiera, Iuliu and Koehler, Viktoria Florentine and Berg, Elke and Kn{\"o}sel, Thomas and Sandner, Benjamin and Fenske, Wiebke Kristin and Bl{\"a}ker, Hendrik and Smaxwil, Constantin and Zielke, Andreas and Sipos, Bence and Allelein, Stephanie and Schott, Matthias and Dierks, Christine and Spitzweg, Christine and Fassnacht, Martin and Kroiss, Matthias}, title = {FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale}, series = {Frontiers in Endocrinology}, volume = {12}, journal = {Frontiers in Endocrinology}, issn = {1664-2392}, doi = {10.3389/fendo.2021.712107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244653}, year = {2021}, abstract = {Background Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising. Materials and Methods Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable. Results PD-L1 TPS≥50\% was observed in 42\% of ATC and 26\% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30\%) than in PDTC (5\%; p<0.01) and NT (0\%, p<0.001). 53\% of PDTC samples had PD-L1 expression ≤5\%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS. Conclusion High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.}, language = {en} }