@article{AdrianMartinezAgeronAharonianetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Ageron, M. and Aharonian, F. and Aiello, S. and Albert, A. and Ameli, F. and Annasontzis, E. and Andre, M. and Androulakis, G. and Anghinolfi, M. and Anton, G. and Ardid, M. and Avgitas, T. and Barbarino, G. and Baret, B. and Barrios-Mart{\´i}, J. and Belhorma, B. and Belias, A. and Berbee, A. and van den Berg, A. and Bertin, V. and Beurthey, S. and van Beeveren, V. and Beverini, N. and Biagi, S. and Biagioni, A. and Billault, M. and Bond{\`i}, M. and Bormuth, R. and Bouhadef, B. and Bourlis, G. and Bourret, S. and Boutonnet, C. and Bouwhuis, M. and Bozza, C. and Bruijn, R. and Brunner, J. and Buis, E. and Busto, J. and Cacopardo, G. and Caillat, L. and Calmai, M. and Calvo, D. and Capone, A. and Caramete, L. and Cecchini, S. and Celli, S. and Champion, C. and Cherkaoui El Moursli, R. and Cherubini, S. and Chiarusi, T. and Circella, M. and Classen, L. and Cocimano, R. and Coelho, J. A. B. and Coleiro, A. and Colonges, S. and Coniglione, R. and Cordelli, M. and Cosquer, A. and Coyle, P. and Creusot, A. and Cuttone, G. and D'Amico, A. and De Bonis, G. and De Rosa, G. and De Sio, C. and Di Capua, F. and Di Palma, I. and D{\´i}az Garc{\´i}a, A. F. and Distefano, C. and Donzaud, C. and Dornic, D. and Dorosti-Hasankiadeh, Q. and Drakopoulou, E. and Drouhin, D. and Drury, L. and Durocher, M. and Eberl, T. and Eichie, S. and van Eijk, D. and El Bojaddaini, I. and El Khayati, N. and Elsaesser, D. and Enzenh{\"o}fer, A. and Fassi, F. and Favali, P. and Fermani, P. and Ferrara, G. and Filippidis, C. and Frascadore, G. and Fusco, L. A. and Gal, T. and Galat{\`a}, S. and Garufi, F. and Gay, P. and Gebyehu, M. and Giordano, V. and Gizani, N. and Gracia, R. and Graf, K. and Gr{\´e}goire, T. and Grella, G. and Habel, R. and Hallmann, S. and van Haren, H. and Harissopulos, S. and Heid, T. and Heijboer, A. and Heine, E. and Henry, S. and Hern{\´a}ndez-Rey, J. J. and Hevinga, M. and Hofest{\"a}dt, J. and Hugon, C. M. F. and Illuminati, G. and James, C. W. and Jansweijer, P. and Jongen, M. and de Jong, M. and Kadler, M. and Kalekin, O. and Kappes, A. and Katz, U. F. and Keller, P. and Kieft, G. and Kießling, D. and Koffeman, E. N. and Kooijman, P. and Kouchner, A. and Kulikovskiy, V. and Lahmann, R. and Lamare, P. and Leisos, A. and Leonora, E. and Lindsey Clark, M. and Liolios, A. and Llorenz Alvarez, C. D. and Lo Presti, D. and L{\"o}hner, H. and Lonardo, A. and Lotze, M. and Loucatos, S. and Maccioni, E. and Mannheim, K. and Margiotta, A. and Marinelli, A. and Mari{\c{s}}, O. and Markou, C. and Mart{\´i}nez-Mora, J. A. and Martini, A. and Mele, R. and Melis, K. W. and Michael, T. and Migliozzi, P. and Migneco, E. and Mijakowski, P. and Miraglia, A. and Mollo, C. M. and Mongelli, M. and Morganti, M. and Moussa, A. and Musico, P. and Musumeci, M. and Navas, S. and Nicoleau, C. A. and Olcina, I. and Olivetto, C. and Orlando, A. and Papaikonomou, A. and Papaleo, R. and Păvăla{\c{s}}, G. E. and Peek, H. and Pellegrino, C. and Perrina, C. and Pfutzner, M. and Piattelli, P. and Pikounis, K. and Poma, G. E. and Popa, V. and Pradier, T. and Pratolongo, F. and P{\"u}hlhofer, G. and Pulvirenti, S. and Quinn, L. and Racca, C. and Raffaelli, F. and Randazzo, N. and Rapidis, P. and Razis, P. and Real, D. and Resvanis, L. and Reubelt, J. and Riccobene, G. and Rossi, C. and Rovelli, A. and Salda{\~n}a, M. and Salvadori, I. and Samtleben, D. F. E. and S{\´a}nchez Garc{\´i}a, A. and S{\´a}nchez Losa, A. and Sanguineti, M. and Santangelo, A. and Santonocito, D. and Sapienza, P. and Schimmel, F. and Schmelling, J. and Sciacca, V. and Sedita, M. and Seitz, T. and Sgura, I. and Simeone, F. and Siotis, I. and Sipala, V. and Spisso, B. and Spurio, M. and Stavropoulos, G. and Steijger, J. and Stellacci, S. M. and Stransky, D. and Taiuti, M. and Tayalati, Y. and T{\´e}zier, D. and Theraube, S. and Thompson, L. and Timmer, P. and T{\"o}nnis, C. and Trasatti, L. and Trovato, A. and Tsirigotis, A. and Tzamarias, S. and Tzamariudaki, E. and Vallage, B. and Van Elewyk, V. and Vermeulen, J. and Vicini, P. and Viola, S. and Vivolo, D. and Volkert, M. and Voulgaris, G. and Wiggers, L. and Wilms, J. and de Wolf, E. and Zachariadou, K. and Zornoza, J. D. and Z{\´u}{\~n}iga, J.}, title = {Letter of intent for KM3NeT 2.0}, series = {Journal of Physics G-Nuclear and Particle Physics}, volume = {43}, journal = {Journal of Physics G-Nuclear and Particle Physics}, number = {8}, doi = {10.1088/0954-3899/43/8/084001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188050}, pages = {84001}, year = {2016}, abstract = {The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and}, language = {en} } @article{BousquetAntoAkdisetal.2016, author = {Bousquet, J. and Anto, J. M. and Akdis, M. and Auffray, C. and Keil, T. and Momas, I. and Postma, D. S. and Valenta, R. and Wickman, M. and Cambon-Thomsen, A. and Haahtela, T. and Lambrecht, B. N. and Lodrup Carlsen, K. C. and Koppelman, G. H. and Sunyer, J. and Zuberbier, T. and Annesi-Maesano, I. and Arno, A. and Bindslev-Jensen, C. and De Carlo, G. and Forastiere, F. and Heinrich, J. and Kowalski, M. L. and Maier, D. and Melen, E. and Palkonen, S. and Smit, H. A. and Standl, M. and Wright, J. and Asarnoj, A. and Benet, M. and Ballardini, N. and Garcia-Aymerich, J. and Gehring, U. and Guerra, S. and Hohman, C. and Kull, I. and Lupinek, C. and Pinart, M. and Skrindo, I. and Westman, M. and Smagghe, D. and Akdis, C. and Albang, R. and Anastasova, V. and Anderson, N. and Bachert, C. and Ballereau, S. and Ballester, F. and Basagana, X. and Bedbrook, A. and Bergstrom, A. and von Berg, A. and Brunekreef, B. and Burte, E. and Carlsen, K.H. and Chatzi, L. and Coquet, J.M. and Curin, M. and Demoly, P. and Eller, E. and Fantini, M.P. and Gerhard, B. and Hammad, H. and von Hertzen, L. and Hovland, V. and Jacquemin, B. and Just, J. and Keller, T. and Kerkhof, M. and Kiss, R. and Kogevinas, M. and Koletzko, S. and Lau, S. and Lehmann, I. and Lemonnier, N. and McEachan, R. and Makela, M. and Mestres, J. and Minina, E. and Mowinckel, P. and Nadif, R. and Nawijn, M. and Oddie, S. and Pellet, J. and Pin, I. and Porta, D. and Ranci{\`e}re, F. and Rial-Sebbag, A. and Schuijs, M.J. and Siroux, V. and Tischer, C.G. and Torrent, M. and Varraso, R. and De Vocht, J. and Wenger, K. and Wieser, S. and Xu, C.}, title = {Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015}, series = {Allergy}, volume = {71}, journal = {Allergy}, number = {11}, doi = {10.1111/all.12880}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186858}, pages = {1513-1525}, year = {2016}, abstract = {MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.}, language = {en} } @article{IyengarSedorFreedmanetal.2015, author = {Iyengar, Sudha K. and Sedor, John R. and Freedman, Barry I. and Kao, W. H. Linda and Kretzler, Matthias and Keller, Benjamin J. and Abboud, Hanna E. and Adler, Sharon G. and Best, Lyle G. and Bowden, Donald W. and Burlock, Allison and Chen, Yii-Der Ida and Cole, Shelley A. and Comeau, Mary E. and Curtis, Jeffrey M. and Divers, Jasmin and Drechsler, Christiane and Duggirala, Ravi and Elston, Robert C. and Guo, Xiuqing and Huang, Huateng and Hoffmann, Michael Marcus and Howard, Barbara V. and Ipp, Eli and Kimmel, Paul L. and Klag, Michael J. and Knowler, William C. and Kohn, Orly F. and Leak, Tennille S. and Leehey, David J. and Li, Man and Malhotra, Alka and M{\"a}rz, Winfried and Nair, Viji and Nelson, Robert G. and Nicholas, Susanne B. and O'Brien, Stephen J. and Pahl, Madeleine V. and Parekh, Rulan S. and Pezzolesi, Marcus G. and Rasooly, Rebekah S. and Rotimi, Charles N. and Rotter, Jerome I. and Schelling, Jeffrey R. and Seldin, Michael F. and Shah, Vallabh O. and Smiles, Adam M. and Smith, Michael W. and Taylor, Kent D. and Thameem, Farook and Thornley-Brown, Denyse P. and Truitt, Barbara J. and Wanner, Christoph and Weil, E. Jennifer and Winkler, Cheryl A. and Zager, Philip G. and Igo, Jr, Robert P. and Hanson, Robert L. and Langefeld, Carl D.}, title = {Genome-wide association and trans-ethnic meta-analysis for advanced diabetic kidney disease: Family Investigation of Nephropathy and Diabetes (FIND)}, series = {PLoS Genetics}, volume = {11}, journal = {PLoS Genetics}, number = {8}, doi = {10.1371/journal.pgen.1005352}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180545}, pages = {e1005352}, year = {2015}, abstract = {Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45\% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10\(^{-9}\)). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10\(^{-8}\)), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.}, language = {en} } @article{FroehlichPinartKelleretal.2017, author = {Fr{\"o}hlich, M. and Pinart, M. and Keller, T. and Reich, A. and Cabieses, B. and Hohmann, C. and Postma, D. S. and Bousquet, J. and Ant{\´o}, J. M. and Keil, T. and Roll, S.}, title = {Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from childhood to adulthood? A meta-analysis}, series = {Clinical and Translational Allergy}, volume = {7}, journal = {Clinical and Translational Allergy}, doi = {10.1186/s13601-017-0176-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172508}, year = {2017}, abstract = {Background: Allergic rhinitis and asthma as single entities affect more boys than girls in childhood but more females in adulthood. However, it is unclear if this prevalence sex-shift also occurs in allergic rhinitis and concurrent asthma. Thus, our aim was to compare sex-specifc differences in the prevalence of coexisting allergic rhinitis and asthma in childhood, adolescence and adulthood. Methods: Post-hoc analysis of systematic review with meta-analysis concerning sex-specific prevalence of allergic rhinitis. Using random-effects meta-analysis, we assessed male-female ratios for coexisting allergic rhinitis and asthma in children (0-10 years), adolescents (11-17) and adults (> 17). Electronic searches were performed using MEDLINE and EMBASE for the time period 2000-2014. We included population-based observational studies, reporting coexisting allergic rhinitis and asthma as outcome stratifed by sex. We excluded non-original or non-population-based studies, studies with only male or female participants or selective patient collectives. Results: From a total of 6539 citations, 10 studies with a total of 93,483 participants met the inclusion criteria. The male-female ratios (95\% CI) for coexisting allergic rhinitis and asthma were 1.65 (1.52; 1.78) in children (N = 6 studies), 0.61 (0.51; 0.72) in adolescents (N = 2) and 1.03 (0.79; 1.35) in adults (N = 2). Male-female ratios for allergic rhinitis only were 1.25 (1.19; 1.32, N = 5) in children, 0.80 (0.71; 0.89, N = 2) in adolescents and 0.98 (0.74; 1.30, N = 2) in adults, respectively. Conclusions: The prevalence of coexisting allergic rhinitis and asthma shows a clear male predominance in childhood and seems to switch to a female predominance in adolescents. This switch was less pronounced for allergic rhinitis only.}, language = {en} } @article{BeningGenserKelleretal.2023, author = {Bening, C. and Genser, B. and Keller, D. and M{\"u}ller-Altrock, S. and Radakovic, D. and Penov, K. and Hassan, M. and Aleksic, I. and Leyh, R. and Madrahimov, N.}, title = {Impact of estradiol, testosterone and their ratio on left and right auricular myofilament function in male and female patients undergoing coronary artery bypass grafting}, series = {BMC Cardiovascular Disorders}, volume = {23}, journal = {BMC Cardiovascular Disorders}, doi = {10.1186/s12872-023-03582-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357368}, year = {2023}, abstract = {Background The impact of sex hormones on right and left auricular contractile apparatus function is largely unknown. We evaluated the impact of sex hormones on left and right heart contractility at the level of myocardial filaments harvested from left and right auricles during elective coronary artery bypass surgery. Methods 150 patients (132 male; 18 female) were enrolled. Preoperative testosterone and estradiol levels were measured with Immunoassay. Calcium induced force measurements were performed with left- and right auricular myofilaments in a skinned fiber model. Correlation analysis was used for comparison of force values and levels of sex hormones and their ratio. Results Low testosterone was associated with higher top force values in right-sided myofilaments but not in left-sided myofilaments for both sexes (p = 0.000 in males, p = 0.001 in females). Low estradiol levels were associated with higher top force values in right-sided myofilaments (p 0.000) in females and only borderline significantly associated with higher top force values in males (p 0.056). In females, low estradiol levels correlated with higher top force values in left sided myofilaments (p 0.000). In males, higher Estradiol/Testosterone ratio (E/T ratio) was only associated with higher top force values from right auricular myofilaments (p 0.04) In contrast, in females higher E/T ratio was associated with lower right auricular myofilament top force values (p 0.03) and higher top force values in left-sided myofilaments (p 0.000). Conclusions This study shows that patients' comorbidities influence left and right sided contractility and may blur results concerning influence of sex hormones if not eliminated. A sex hormone dependent influence is obvious with different effects on the left and right ventricle. The E/T ratio and its impact on myofilament top force showed divergent results between genders, and may partially explain gender differences in patients with cardiovascular disease.}, language = {en} } @article{VillalobosWieseImhoffetal.2019, author = {Villalobos, Alvaro S. and Wiese, Jutta and Imhoff, Johannes F. and Dorador, Cristina and Keller, Alexander and Hentschel, Ute}, title = {Systematic affiliation and genome analysis of Subtercola vilae DB165T with particular emphasis on cold adaptation of an isolate from a high-altitude cold volcano lake}, series = {Microorganisms}, volume = {7}, journal = {Microorganisms}, number = {4}, issn = {2076-2607}, doi = {10.3390/microorganisms7040107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197394}, year = {2019}, abstract = {Among the Microbacteriaceae the species of Subtercola and Agreia form closely associated clusters. Phylogenetic analysis demonstrated three major phylogenetic branches of these species. One of these branches contains the two psychrophilic species Subtercola frigoramans and Subtercola vilae, together with a larger number of isolates from various cold environments. Genomic evidence supports the separation of Agreia and Subtercola species. In order to gain insight into the ability of S. vilae to adapt to life in this extreme environment, we analyzed the genome with a particular focus on properties related to possible adaptation to a cold environment. General properties of the genome are presented, including carbon and energy metabolism, as well as secondary metabolite production. The repertoire of genes in the genome of S. vilae DB165\(^T\) linked to adaptations to the harsh conditions found in Llullaillaco Volcano Lake includes several mechanisms to transcribe proteins under low temperatures, such as a high number of tRNAs and cold shock proteins. In addition, S. vilae DB165\(^T\) is capable of producing a number of proteins to cope with oxidative stress, which is of particular relevance at low temperature environments, in which reactive oxygen species are more abundant. Most important, it obtains capacities to produce cryo-protectants, and to combat against ice crystal formation, it produces ice-binding proteins. Two new ice-binding proteins were identified which are unique to S. vilae DB165\(^T\). These results indicate that S. vilae has the capacity to employ different mechanisms to live under the extreme and cold conditions prevalent in Llullaillaco Volcano Lake.}, language = {en} } @article{MahyeraSchneiderHalligerKelleretal.2018, author = {Mahyera, Alexis S. and Schneider, Tamara and Halliger-Keller, Birgit and Schrooten, Katja and H{\"o}rner, Eva-Maria and Rost, Simone and Kress, Wolfram}, title = {Distribution and Structure of DM2 Repeat Tract Alleles in the German Population}, series = {Frontiers in Neurology}, volume = {9}, journal = {Frontiers in Neurology}, number = {463}, issn = {1664-2295}, doi = {10.3389/fneur.2018.00463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196252}, year = {2018}, abstract = {Autosomal dominant inherited Myotonic dystrophy type 1 and 2 (DM1 and DM2) are the most frequent muscle dystrophies in the European population and are caused by repeat expansion mutations. For Germany cumulative empiric evidence suggests an estimated prevalence of DM2 of roughly 9 in 100,000, therefore being as prevalent as DM1. In DM2, a (CCTG)n repeat tract located in the first intron of the CNBP gene is expanded. The CCTG repeat tract is part of a complex repeat structure comprising not only CCTG tetraplets but also repeated TG dinucleotides and TCTG tetraplet elements as well as NCTG interruptions. Here, we provide the distribution of normal sized alleles in the German population, which was found to be highly similar to the Slovak population. Sequencing of 34 unexpanded healthy range alleles in DM2 positive patients (heterozygous for a full expansion) revealed that the CCTG repeat tract is usually interrupted by at least three tetraplets which according to current opinion is supposed to render it stable against expansion. Interestingly, only the largest analyzed normal allele had 23 uninterrupted CCTGs and consequently could represent an instable early premutation allele. In our diagnostic history of DM2 cases, a total of 18 premutations were detected in 16 independent cases. Here, we describe two premutation families, one with an expansion from a premutation allele and the other with a contraction of a full expansion down to a premutation allele. Our diagnostic results support the general assumption that the premutation range of unstable CCTG stretches lies obviously between 25 and 75 CCTGs. However, the clinical significance of premutation alleles is still unclear. In the light of the two described families we suggest incomplete penetrance. Thus, as it was proposed for other repeat expansion diseases (e.g., Huntington's disease), a fluid transition of penetrance is more likely rather than a clear cut CCTG number threshold.}, language = {en} } @article{LieseSchoenvanderLindenetal.2019, author = {Liese, J. G. and Schoen, C. and van der Linden, M. and Lehmann, L. and Goettler, D. and Keller, S. and Maier, A. and Segerer, F. and Rose, M. A. and Streng, A.}, title = {Changes in the incidence and bacterial aetiology of paediatric parapneumonic pleural effusions/empyema in Germany, 2010-2017: a nationwide surveillance study}, series = {Clinical Microbiology and Infection}, volume = {25}, journal = {Clinical Microbiology and Infection}, doi = {10.1016/j.cmi.2018.10.020}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236866}, pages = {857-864}, year = {2019}, abstract = {Objectives Parapneumonic pleural effusions/empyema (PPE/PE) are severe complications of community-acquired pneumonia. We investigated the bacterial aetiology and incidence of paediatric PPE/PE in Germany after the introduction of universal pneumococcal conjugate vaccine (PCV) immunization for infants. Methods Children <18 years of age hospitalized with pneumonia-associated PPE/PE necessitating pleural drainage or persisting >7 days were reported to the German Surveillance Unit for Rare Diseases in Childhood between October 2010 and June 2017. All bacteria detected in blood or pleural fluid (by culture/PCR) were included, with serotyping for Streptococcus pneumoniae. Results The median age of all 1447 PPE/PE patients was 5 years (interquartile range 3-10). In 488 of the 1447 children with PPE/PE (34\%), 541 bacteria (>40 species) were detected. Aerobic gram-positive cocci accounted for 469 of 541 bacteria detected (87\%); these were most frequently Streptococcus pneumoniae (41\%), Streptococcus pyogenes (19\%) and Staphylococcus aureus (6\%). Serotype 3 accounted for 45\% of 78 serotyped S. pneumoniae strains. Annual PPE/PE incidence varied between 14 (95\%CI 12-16) and 18 (95\%CI 16-21) PPE/PE per million children. Incidence of S. pneumoniae PPE/PE decreased from 3.5 (95\%CI 2.5-4.6) per million children in 2010/11 to 1.5 (95\%CI 0.9-2.4) in 2013/14 (p 0.002), followed by a re-increase to 2.2 (95\%CI 1.5-3.2) by 2016/17 (p 0.205). Conclusions In the era of widespread PCV immunization, cases of paediatric PPE/PE were still caused mainly by S. pneumoniae and, increasingly, by S. pyogenes. The re-increase in the incidence of PPE/PE overall and in S. pneumoniae-associated PPE/PE indicates ongoing changes in the bacterial aetiology and requires further surveillance.}, language = {en} }