TY - JOUR A1 - Westbury, Sarah K A1 - Turro, Ernest A1 - Greene, Daniel A1 - Lentaigne, Claire A1 - Kelly, Anne M A1 - Bariana, Tadbir K A1 - Simeoni, Ilenia A1 - Pillois, Xavier A1 - Attwood, Antony A1 - Austin, Steve A1 - Jansen, Sjoert BG A1 - Bakchoul, Tamam A1 - Crisp-Hihn, Abi A1 - Erber, Wendy N A1 - Favier, Rémi A1 - Foad, Nicola A1 - Gattens, Michael A1 - Jolley, Jennifer D A1 - Liesner, Ri A1 - Meacham, Stuart A1 - Millar, Carolyn M A1 - Nurden, Alan T A1 - Peerlinck, Kathelijne A1 - Perry, David J A1 - Poudel, Pawan A1 - Schulman, Sol A1 - Schulze, Harald A1 - Stephens, Jonathan C A1 - Furie, Bruce A1 - Robinson, Peter N A1 - van Geet, Chris A1 - Rendon, Augusto A1 - Gomez, Keith A1 - Laffan, Michael A A1 - Lambert, Michele P A1 - Nurden, Paquita A1 - Ouwehand, Willem H A1 - Richardson, Sylvia A1 - Mumford, Andrew D A1 - Freson, Kathleen T1 - Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders JF - Genome Medicine N2 - Background: Heritable bleeding and platelet disorders (BPD) are heterogeneous and frequently have an unknown genetic basis. The BRIDGE-BPD study aims to discover new causal genes for BPD by high throughput sequencing using cluster analyses based on improved and standardised deep, multi-system phenotyping of cases. Methods: We report a new approach in which the clinical and laboratory characteristics of BPD cases are annotated with adapted Human Phenotype Ontology (HPO) terms. Cluster analyses are then used to characterise groups of cases with similar HPO terms and variants in the same genes. Results: We show that 60% of index cases with heritable BPD enrolled at 10 European or US centres were annotated with HPO terms indicating abnormalities in organ systems other than blood or blood-forming tissues, particularly the nervous system. Cases within pedigrees clustered closely together on the bases of their HPO-coded phenotypes, as did cases sharing several clinically suspected syndromic disorders. Cases subsequently found to harbour variants in ACTN1 also clustered closely, even though diagnosis of this recently described disorder was not possible using only the clinical and laboratory data available to the enrolling clinician. Conclusions: These findings validate our novel HPO-based phenotype clustering methodology for known BPD, thus providing a new discovery tool for BPD of unknown genetic basis. This approach will also be relevant for other rare diseases with significant genetic heterogeneity. KW - disease KW - thrombocytopenia KW - guidelines KW - complex Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143329 VL - 7 IS - 36 ER - TY - JOUR A1 - Schreiber, Olivia A1 - Schneiderat, Peter A1 - Kress, Wolfram A1 - Rautenstrauss, Bernd A1 - Senderek, Jan A1 - Schoser, Bendikt A1 - Walter, Maggie C. T1 - Facioscapulohumeral muscular dystrophy and Charcot-Marie-Tooth neuropathy 1A-evidence for "double trouble" overlapping syndromes JF - BMC Medical Genetics N2 - Background: We report on a patient with genetically confirmed overlapping diagnoses of CMT1A and FSHD. This case adds to the increasing number of unique patients presenting with atypical phenotypes, particularly in FSHD. Even if a mutation in one disease gene has been found, further genetic testing might be warranted in cases with unusual clinical presentation. Case presentation: The reported 53 years old male patient suffered from walking difficulties and foot deformities first noticed at age 20. Later on, he developed scapuloperoneal and truncal muscle weakness, along with atrophy of the intrinsic hand and foot muscles, pes cavus, claw toes and a distal symmetric hypoesthesia. Motor nerve conduction velocities were reduced to 20 m/s in the upper extremities, and not educible in the lower extremities, sensory nerve conduction velocities were not attainable. Electromyography showed both, myopathic and neurogenic changes. A muscle biopsy taken from the tibialis anterior muscle showed a mild myopathy with some neurogenic findings and hypertrophic type 1 fibers. Whole-body muscle MRI revealed severe changes in the lower leg muscles, tibialis anterior and gastrocnemius muscles were highly replaced by fatty tissue. Additionally, fatty degeneration of shoulder girdle and straight back muscles, and atrophy of dorsal upper leg muscles were seen. Taken together, the presenting features suggested both, a neuropathy and a myopathy. Patient's family history suggested an autosomal dominant inheritance. Molecular testing revealed both, a hereditary motor and sensory neuropathy type 1A (HMSN1A, also called Charcot-Marie-Tooth neuropathy 1A, CMT1A) due to a PMP22 gene duplication and facioscapulohumeral muscular dystrophy (FSHD) due to a partial deletion of the D4Z4 locus (19 kb). Conclusion: Molecular testing in hereditary neuromuscular disorders has led to the identification of an increasing number of atypical phenotypes. Nevertheless, finding the right diagnosis is crucial for the patient in order to obtain adequate medical care and appropriate genetic counseling, especially in the background of arising curative therapies. KW - D4Z4 partial deletion KW - sensory neuropathy KW - hereditary motor KW - disease KW - phenotype KW - FSHD KW - myopathy KW - patient KW - duplication KW - diagnosis KW - facioscapulohumeral muscular dystrophy KW - Charcot-Marie-Tooth neuropathy 1A KW - hereditary motor and sensory neuropathy KW - double trouble KW - overlapping syndrome Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121963 SN - 1471-2350 VL - 14 IS - 92 ER - TY - JOUR A1 - Schlagenhauf, Ulrich A1 - Jakob, Lena A1 - Eigenthaler, Martin A1 - Segerer, Sabine A1 - Jockel-Schneider, Yvonne A1 - Rehn, Monika T1 - Regular consumption of Lactobacillus reuteri-containing lozenges reduces pregnancy gingivitis: an RCT JF - Journal of Clinical Periodontology N2 - Aim: This randomized controlled trial assessed the impact of Lactobacillus reuteri on pregnancy gingivitis in healthy women. Materials and Methods: Forty-five healthy women (24 test/21 placebo) with pregnancy gingivitis in the third trimester of pregnancy were enrolled. At baseline Gingival Index (GI) and Plaque Index (PlI) were assessed at the Ramfjord teeth and venous blood taken for TNF-alpha analysis. Subsequently participants were randomly provided with lozenges to be consumed 2 9 daily until birth (approx. 7 weeks) containing >= 10(8) CFU L. reuteri ATCC PTA 5289 and >= 10(8) CFU L. reuteri DSM 17938 (test) or being devoid of L. reuteri (placebo). Within 2 days after birth recording of GI, PlI and blood sampling were repeated. Results: At baseline, mean GI and mean PlI did not differ significantly between both groups. In the test group mean TNF-alpha serum level was significantly (p < 0.02) lower than in the placebo group. At reevaluation, mean GI and mean PlI of the test group were both significantly (p < 0.0001) lower than in the placebo group. Mean TNF-alpha serum level did no longer differ significantly between the groups. Conclusions: The consumption of L. reuteri lozenges may be a useful adjunct in the control of pregnancy gingivitis. KW - chronic periodontitis KW - probiotic lozenges KW - subgingival KW - bacteria KW - postpartum KW - microbiota KW - disease KW - L. reuteri KW - plaque KW - pregnancy KW - pregnancy gingivitis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186783 VL - 43 IS - 11 ER - TY - JOUR A1 - Sauerbrei, A. A1 - Langenhan, T. A1 - Brandstädt, A. A1 - Schmidt-Ott, R. A1 - Krumbholz, A. A1 - Girschick, H. A1 - Huppertz, H. A1 - Kaiser, P. A1 - Liese, J. A1 - Streng, A. A1 - Niehues, T. A1 - Peters, J. A1 - Sauerbrey, A. A1 - Schroten, H. A1 - Tenenbaum, T. A1 - Wirth, S. A1 - Wutzler, P. T1 - Prevalence of antibodies against influenza A and B viruses in children in Germany, 2008 to 2010 JF - Eurosurveillance N2 - The prevalence of influenza A and B virus-specific IgG was determined in sera taken between 2008 and 2010 from 1,665 children aged 0-17 years and 400 blood donors in Germany. ELISA on the basis of whole virus antigens was applied. Nearly all children aged nine years and older had antibodies against influenza A. In contrast, 40% of children aged 0-4 years did not have any influenza A virus-specific IgG antibodies. Eighty-six percent of 0-6 year-olds, 47% of 7-12 year-olds and 20% of 13-17 year-olds were serologically naive to influenza B viruses. By the age of 18 years, influenza B seroprevalence reached approximately 90%. There were obvious regional differences in the seroprevalence of influenza B in Germany. In conclusion, seroprevalences of influenza A and influenza B increase gradually during childhood. The majority of children older than eight years have basal immunity to influenza A, while comparable immunity against influenza B is only acquired at the age of 18 years. Children aged 0-6 years, showing an overall seroprevalence of 67% for influenza A and of 14% for influenza B, are especially at risk for primary infections during influenza B seasons. KW - disease KW - healthy children KW - vaccine KW - burden KW - hospitalizations KW - efficacy Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117347 SN - 1560-7917 VL - 19 IS - 5 ER - TY - JOUR A1 - Rovituso, Damiano M. A1 - Duffy, Catharina E. A1 - Schroeter, Michael A1 - Kaiser, Claudia C. A1 - Kleinschnitz, Christoph A1 - Bayas, Antonios A1 - Elsner, Rebecca A1 - Kuerten, Stefanie T1 - The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients JF - Scientific Reports N2 - B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to brain antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that patients can be subdivided into responders that show brain-specific B cell reactivity in the blood and patients without this reactivity. Only in patients that classified as B cell responders, there was a significant positive correlation between treatment duration and the time since last relapse in our study. This correlation was GA-specific because it was absent in a control group that consisted of interferon-\(\beta\) (IFN-\(\beta\))-treated RRMS patients (n = 23). These data suggest that GA has an effect on brain-reactive B cells in a subset of patients and that only this subset benefits from treatment. The detection of brain-reactive B cells is likely to be a suitable tool to identify drug responders. KW - cortical pathology KW - natural history KW - disability KW - expression KW - antibodies KW - disease KW - lesions KW - trial KW - multiple sclerosis Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148172 VL - 5 IS - 14265 ER - TY - JOUR A1 - Rose, Markus A. A1 - Damm, Oliver A1 - Greiner, Wolfgang A1 - Knuf, Markus A1 - Wutzler, Peter A1 - Liese, Johannes G. A1 - Krüger, Hagen A1 - Wahn, Ulrich A1 - Schaberg, Tom A1 - Schwehm, Markus A1 - Kochmann, Thomas F. A1 - Eichner, Martin T1 - The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study JF - BMC Infectious Diseases N2 - Background: Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. Methods: A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. Results: In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Conclusions: Our results demonstrate that vaccinating children 2-17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany. KW - vaccination KW - live-attenuated influenza vaccine KW - children KW - transmission model KW - metanalysis KW - recommendations KW - hospitalizations KW - burden KW - infection KW - young children KW - seasonal influenza KW - United States KW - disease KW - efficacy KW - Germany KW - influenza Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117563 SN - 1471-2334 VL - 14 IS - 40 ER - TY - JOUR A1 - Okoro, Chinyere K. A1 - Barquist, Lars A1 - Connor, Thomas R. A1 - Harris, Simon R. A1 - Clare, Simon A1 - Stevens, Mark P. A1 - Arends, Mark J. A1 - Hale, Christine A1 - Kane, Leanne A1 - Pickard, Derek J. A1 - Hill, Jennifer A1 - Harcourt, Katherine A1 - Parkhill, Julian A1 - Dougan, Gordon A1 - Kingsley, Robert A. T1 - Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa JF - PLoS Neglected Tropical Diseases N2 - Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population. KW - genome sequence KW - infection KW - pathogenicity KW - children KW - disease KW - adults KW - identification KW - Escherichia coli KW - virulence Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143779 VL - 9 IS - 3 ER - TY - JOUR A1 - Naseem, Muhammad A1 - Dandekar, Thomas T1 - The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions JF - PLOS Pathogens N2 - No abstract available. KW - disease KW - pseudomas-syringae KW - arabidpsis thaliana KW - immunity KW - organogenesis KW - transcription KW - resistance KW - crosstalk Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131901 VL - 8 IS - 11 ER - TY - JOUR A1 - Müller, Stefanie H. A1 - Girard, Simon L. A1 - Hopfner, Franziska A1 - Merner, Nancy D. A1 - Bourassa, Cynthia V. A1 - Lorenz, Delia A1 - Clark, Lorraine N. A1 - Tittmann, Lukas A1 - Soto-Ortolaza, Alexandra I. A1 - Klebe, Stephan A1 - Hallett, Mark A1 - Schneider, Susanne A. A1 - Hodgkinson, Colin A. A1 - Lieb, Wolfgang A1 - Wszolek, Zbigniew K. A1 - Pendziwiat, Manuela A1 - Lorenzo-Betancor, Oswaldo A1 - Poewe, Werner A1 - Ortega-Cubero, Sara A1 - Seppi, Klaus A1 - Rajput, Alex A1 - Hussl, Anna A1 - Rajput, Ali H. A1 - Berg, Daniela A1 - Dion, Patrick A. A1 - Wurster, Isabel A1 - Shulman, Joshua M. A1 - Srulijes, Karin A1 - Haubenberger, Dietrich A1 - Pastor, Pau A1 - Vilariño-Güell, Carles A1 - Postuma, Ronald B. A1 - Bernard, Geneviève A1 - Ladwig, Karl-Heinz A1 - Dupré, Nicolas A1 - Jankovic, Joseph A1 - Strauch, Konstantin A1 - Panisset, Michel A1 - Winkelmann, Juliane A1 - Testa, Claudia M. A1 - Reischl, Eva A1 - Zeuner, Kirsten E. A1 - Ross, Owen A. A1 - Arzberger, Thomas A1 - Chouinard, Sylvain A1 - Deuschl, Günther A1 - Louis, Elan D. A1 - Kuhlenbäumer, Gregor A1 - Rouleau, Guy A. T1 - Genome-wide association study in essential tremor identifies three new loci JF - Brain N2 - 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. KW - quality-control KW - disease KW - tool KW - movement disorders KW - genome-wide association study KW - tremor KW - genetics KW - essential tremor Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186541 VL - 139 ER - TY - JOUR A1 - Leistner, Stefanie A1 - Benik, Steffen A1 - Laumeier, Inga A1 - Ziegler, Annerose A1 - Nieweler, Gabriele A1 - Nolte, Christian H. A1 - Heuschmann, Peter U. A1 - Audebert, Heinrich J. T1 - Secondary Prevention after Minor Stroke and TIA - Usual Care and Development of a Support Program JF - PLoS One N2 - Background: Effective methods of secondary prevention after stroke or TIA are available but adherence to recommended evidence-based treatments is often poor. The study aimed to determine the quality of secondary prevention in usual care and to develop a stepwise modeled support program. Methods: Two consecutive cohorts of patients with acute minor stroke or TIA undergoing usual outpatient care versus a secondary prevention program were compared. Risk factor control and medication adherence were assessed in 6-month follow-ups (6M-FU). Usual care consisted of detailed information concerning vascular risk factor targets given at discharge and regular outpatient care by primary care physicians. The stepwise modeled support program additionally employed up to four outpatient appointments. A combination of educational and behavioral strategies was employed. Results: 168 patients in the observational cohort who stated their openness to participate in a prevention program (mean age 64.7 y, admission blood pressure (BP): 155/84 mmHg) and 173 patients participating in the support program (mean age 67.6 y, BP: 161/84 mmHg) were assessed at 6 months. Proportions of patients with BP according to guidelines were 50% in usual-care and 77% in the support program (p<0.01). LDL<100 mg/dl was measured in 62 versus 71% (p = 0.12). Proportions of patients who stopped smoking were 50 versus 79% (p<0.01). 72 versus 89% of patients with atrial fibrillation were on oral anticoagulation (p = 0.09). Conclusions: Risk factor control remains unsatisfactory in usual care. Targets of secondary prevention were met more often within the supported cohort. Effects on (cerebro-)vascular recurrence rates are going to be assessed in a multicenter randomized trial. KW - atherothrombosis KW - multifactorial KW - clinical trial KW - hypertension KW - disease KW - transient ischemic attack KW - randomized controlled trial KW - cardiovascular risk factors KW - blood pressure KW - event rates Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135247 VL - 7 IS - 12 ER - TY - JOUR A1 - Kölligan, Daniel T1 - Murmur, heat and bonds – on some words of magic and healing JF - Indogermanische Forschungen N2 - The paper argues that a) Germanic *tauf/ƀra- (Germ. Zauber, etc.) is related to a root PIE *deu̯p- ‘beat; make a hollow sound, resound’ found in Greek δοῦπος ‘thud’, etc., b) Greek φάρμακον goes back to the root PIE *gʷʰer- ‘heat’ (Gk. θερμός, etc.) implying healing by fomentation, and c) Armenian hiwand ‘sick’, borrowed from Iranian, to PIE *sh₂ei̯- ‘bind’ relying on the notion of disease as a supernatural bond. KW - magic KW - spell KW - healing KW - disease KW - lexicon KW - etymology Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250976 SN - 1613-0405 SN - 0019-7262 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 126 IS - 1 SP - 107 EP - 134 ER - TY - JOUR A1 - Kölligan, Daniel T1 - A note on Vedic cīti- JF - Indogermanische Forschungen N2 - Vedic cīti-, attested in the Atharvaveda, is argued to be related to Av. ṣ̌āitī-, OP šiyāti- ‘happiness’ built to PIE *kʷi̯eh₁- ‘to (come to) rest’. KW - Vedic KW - Atharvaveda KW - disease KW - healing KW - etymology Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250986 SN - 1613-0405 SN - 0019-7262 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 126 IS - 1 SP - 135 EP - 140 ER - TY - JOUR A1 - Krämer, Johannes A1 - Bijnens, Bart A1 - Störk, Stefan A1 - Ritter, Christian O. A1 - Liu, Dan A1 - Ertl, Georg A1 - Wanner, Christoph A1 - Weidemann, Frank T1 - Left ventricular geometry and blood pressure as predictors of adverse progression of Fabry cardiomyopathy JF - PLoS ONE N2 - Background In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated. Methods In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed. Results Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05). Conclusions LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy. KW - cardiovascular magnetic resonance KW - clinical manifestations KW - disease KW - identification KW - fibrosis KW - 2-dimensional speckle tracking KW - myocardial infarction KW - therapy KW - diagnosis KW - impact Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145131 VL - 10 IS - 11 ER - TY - JOUR A1 - Konrad, Franziska M. A1 - Bury, Annette A1 - Schick, Martin A. A1 - Ngamsri, Kristian-Christos A1 - Reutershan, Jörg T1 - The Unrecognized Effects of Phosphodiesterase 4 on Epithelial Cells in Pulmonary Inflammation JF - PLoS ONE N2 - Acute pulmonary inflammation is characterized by migration of polymorphonuclear neutrophils (PMNs) into the different compartments of the lung, passing an endothelial and epithelial barrier. Recent studies showed evidence that phosphodiesterase (PDE) 4-inhibitors stabilized endothelial cells. PDE4B and PDE4D subtypes play a pivotal role in inflammation, whereas blocking PDE4D is suspected to cause gastrointestinal side effects. We thought to investigate the particular role of the PDE4-inhibitors roflumilast and rolipram on lung epithelium. Acute pulmonary inflammation was induced by inhalation of LPS. PDE4-inhibitors were administered i.p. or nebulized after inflammation. The impact of PDE4-inhibitors on PMN migration was evaluated in vivo and in vitro. Microvascular permeability, cytokine levels, and PDE4B and PDE4D expression were analyzed. In vivo, both PDE4-inhibitors decreased transendothelial and transepithelial migration even when administered after inflammation, whereas roflumilast showed a superior effect compared to rolipram on the epithelium. Both inhibitors decreased TNF\(\alpha\), IL6, and CXCL2/3. CXCL1, the strong PMN chemoattractant secreted by the epithelium, was significantly more reduced by roflumilast. In vitro assays with human epithelium also emphasized the pivotal role of roflumilast on the epithelium. Additionally, LPS-induced stress fibers, an essential requirement for a direct migration of PMNs into the alveolar space, were predominantly reduced by roflumilast. Expression of PDE4B and PDE4D were both increased in the lungs by LPS, PDE4-inhibitors decreased mainly PDE4B. The topical administration of PDE4-inhibitors was also effective in curbing down PMN migration, further highlighting the clinical potential of these compounds. In pulmonary epithelial cells, both subtypes were found coexistent around the nucleus and the cytoplasm. In these epithelial cells, LPS increased PDE4B and, to a lesser extend, PDE4D, whereas the effect of the inhibitors was prominent on the PDE4B subtype. In conclusion, we determined the pivotal role of the PDE4-inhibitor roflumilast on lung epithelium and emphasized its main effect on PDE4B in hyperinflammation. KW - acute lung injury KW - PDE4-inhibitor roflumilast KW - GRO alpha KW - expression KW - 4D KW - respiratory distress syndrome KW - mice KW - infiltration KW - rolipram KW - disease Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143203 VL - 10 IS - 4 ER - TY - JOUR A1 - Keller, Andreas A1 - Leidinger, Petra A1 - Vogel, Britta A1 - Backes, Christina A1 - ElSharawy, Abdou A1 - Galata, Valentina A1 - Mueller, Sabine C. A1 - Marquart, Sabine A1 - Schrauder, Michael G. A1 - Strick, Reiner A1 - Bauer, Andrea A1 - Wischhusen, Jörg A1 - Beier, Markus A1 - Kohlhaas, Jochen A1 - Katus, Hugo A. A1 - Hoheisel, Jörg A1 - Franke, Andre A1 - Meder, Benjamin A1 - Meese, Eckart T1 - miRNAs can be generally associated with human pathologies as exemplified for miR-144* JF - BMC MEDICINE N2 - Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 ( 95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers. KW - peripheral blood KW - microna profiles KW - disease KW - signature KW - expression KW - miRNA KW - microarray KW - biomarker KW - bioinformatics KW - lung-cancer KW - multiple sclerosis KW - gene KW - serum Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114349 SN - 1741-7015 VL - 12 ER - TY - JOUR A1 - Jain, Preetesh A1 - Javdan, Mohammad A1 - Feger, Franziska K. A1 - Chiu, Pui Yan A1 - Sison, Cristina A1 - Damle, Rajendra N. A1 - Bhuiya, Tawfiqul A. A1 - Sen, Filiz A1 - Abruzzo, Lynne V. A1 - Burger, Jan A. A1 - Rosenwald, Andreas A1 - Allen, Steven L. A1 - Kolitz, Jonathan E. A1 - Rai, Kanti R. A1 - Chiorazzi, Nicholas A1 - Sherry, Barbara T1 - Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance JF - Haematologica N2 - Background The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome. Design and Methods: Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence. Results: The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two "non-Th17" interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells. Conclusions: Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study. KW - disease KW - helper T cells KW - T(H)17 cells KW - tumor microenvironment KW - multiple myeloma KW - up regulation KW - mast cells KW - lineage KW - pathway KW - IL-17 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131290 VL - 97 IS - 4 ER - TY - JOUR A1 - Isaias, Ioannis U. A1 - Marzegan, Alberto A1 - Pezzoli, Gianni A1 - Marotta, Giorgio A1 - Canesi, Margherita A1 - Biella, Gabriele E. M. A1 - Volkmann, Jens A1 - Cavallari, Paolo T1 - A role for locus coeruleus in Parkinson tremor JF - Frontiers in Human Neuroscience N2 - We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease(PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [\(^{123}\)I] N-\(\omega\)-fluoropropyl-2 \(\beta\)-carbomethoxy-3 \(\beta\)-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor. KW - locus coeruleus KW - disease KW - basal ganglia KW - resting tremor KW - functional neuroanatomy KW - dopamine KW - norepinephrine KW - progression KW - binding KW - rat KW - noradrenalin KW - parkinson disease KW - tremor Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133955 VL - 5 IS - 179 ER - TY - THES A1 - Hempel, Katharina T1 - Vergleichende Analyse von Antigenexpressionsmustern kindlicher cALL-Blasten und gesunden B-Zellvorstufen – Nutzen für die MRD Diagnostik T1 - Comparative analysis of antigen expression on cALL blasts and healthy B cell progenitors – Use for MRD diagnostics N2 - Die MRD Diagnostik ist von erheblicher Bedeutung für die Risikostratifizierung kindlicher Leukämien. Um aber gesunde, sich regenerierende Vorstufen von blastären Zellen unterscheiden zu können ist die genaue Kenntnis des Antigenverlaufs sowohl der Vorstufen der B-Zellreihe als auch der Blasten notwendig. In dieser Arbeit wird eine Vergleichende Analyse von B-Zellvorstufen und Blasten mittels Durchflusszytometrie durchgeführt. Von besonders diskriminativem Wert waren die Vorläufermarker CD10, CD34, sowie die lymphatischen Marker CD19, CD20, CD22, CD45, cyCD79a und cyTdT. Zur Beschreibung des individuellen LAIP eigneten sich vor allem die Marker CD11b, CD38, CD58, CD123 und CD133, sowie die myeloischen Marker CD13 und CD33. Die Bessere Unterscheidung zwischen gesunden und kranken Zellen zusammen mit neuen Entwicklungen in Diagnostik und Therapie muss in Zukunft zur weiteren Verbesserung der Überlebensraten, auch im Rezidiv führen. N2 - MRD diagnostic is important for the ongoing therapy of cALL in children. For better discrimination between blasts and b-cell progenitors we used flow cytometry to analyse the antigen expression on b cell progenitors with those on cALL blasts. KW - residual KW - minimal KW - disease KW - Durchflusszytometrie KW - Akute Leukämie KW - MRD KW - kindliche Leukämie KW - cALL Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179203 ER - TY - JOUR A1 - Hedrich, Christian M. A1 - Hofmann, Sigrun R. A1 - Pablik, Jessica A1 - Morbach, Henner A1 - Girschick, Hermann J. T1 - Autoinflammatory bone disorders with special focus on chronic recurrent multifocal osteomyelitis (CRMO) JF - Pediatric Rheumatology N2 - Sterile bone inflammation is the hallmark of autoinflammatory bone disorders, including chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO). Autoinflammatory osteopathies are the result of a dysregulated innate immune system, resulting in immune cell infiltration of the bone and subsequent osteoclast differentiation and activation. Interestingly, autoinflammatory bone disorders are associated with inflammation of the skin and/or the intestine. In several monogenic autoinflammatory bone disorders mutations in disease-causing genes have been reported. However, regardless of recent developments, the molecular pathogenesis of CNO/CRMO remains unclear. Here, we discuss the clinical presentation and molecular pathophysiology of human autoinflammatory osteopathies and animal models with special focus on CNO/CRMO. Treatment options in monogenic autoinflammatory bone disorders and CRMO will be illustrated. KW - bisphosphonate treatment KW - IL-10 expression KW - TNF-α KW - IL-10 KW - inflammation KW - bone KW - CRMO KW - CNO KW - DIRA KW - PAPA KW - Majeed-Syndrome KW - disease KW - deficiency KW - pediatric patients KW - treatment KW - TLR4 KW - PAPA syndrome KW - hypertrophic osteodystrophy KW - chronic nonbacterial osteomyelitis KW - congenital dyserythropoietic anemia Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125694 SN - 1546-0096 VL - 11 IS - 47 ER - TY - JOUR A1 - Grabenhenrich, Linus B. A1 - Reich, Andreas A1 - Fischer, Felix A1 - Zepp, Fred A1 - Forster, Johannes A1 - Schuster, Antje A1 - Bauer, Carl-Peter A1 - Bergmann, Renate L. A1 - Bergmann, Karl E. A1 - Wahn, Ulrich A1 - Keil, Thomas A1 - Lau, Susanne T1 - The Novel 10-Item Asthma Prediction Tool: External Validation in the German MAS Birth Cohort JF - PLOS ONE N2 - Background: A novel non-invasive asthma prediction tool from the Leicester Cohort, UK, forecasts asthma at age 8 years based on 10 predictors assessed in early childhood, including current respiratory symptoms, eczema, and parental history of asthma. Objective: We aimed to externally validate the proposed asthma prediction method in a German birth cohort. Methods: The MAS-90 study (Multicentre Allergy Study) recorded details on allergic diseases prospectively in about yearly follow-up assessments up to age 20 years in a cohort of 1,314 children born 1990. We replicated the scoring method from the Leicester cohort and assessed prediction, performance and discrimination. The primary outcome was defined as the combination of parent-reported wheeze and asthma drugs (both in last 12 months) at age 8. Sensitivity analyses assessed model performance for outcomes related to asthma up to age 20 years. Results: For 140 children parents reported current wheeze or cough at age 3 years. Score distribution and frequencies of later asthma resembled the Leicester cohort: 9% vs. 16% (MAS-90 vs. Leicester) of children at low risk at 3 years had asthma at 8 years, at medium risk 45% vs. 48%. Performance of the asthma prediction tool in the MAS-90 cohort was similar (Brier score 0.22 vs. 0.23) and discrimination slightly better than in the original cohort (area under the curve, AUC 0.83 vs. 0.78). Prediction and discrimination were robust against changes of inclusion criteria, scoring and outcome definitions. The secondary outcome 'physicians' diagnosed asthma at 20 years' showed the highest discrimination (AUC 0.89). Conclusion: The novel asthma prediction tool from the Leicester cohort, UK, performed well in another population, a German birth cohort, supporting its use and further development as a simple aid to predict asthma risk in clinical settings. KW - disease KW - models KW - symptoms KW - risk KW - early-life KW - young children KW - preschool children KW - sample KW - wheeze KW - age Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114202 SN - 1932-6203 VL - 9 IS - 12 ER - TY - JOUR A1 - Dasenbrook, Elliot C. A1 - Lu, Luan A1 - Donnola, Shannon A1 - Weaver, David E. A1 - Gulani, Viskas A1 - Jakob, Peter M. A1 - Konstan, Michael W. A1 - Flask, Chris A. T1 - Normalized T1 Magnetic Resonance Imaging for Assessment of Regional Lung Function in Adult Cystic Fibrosis Patients - A Cross-Sectional Study JF - PLOS ONE N2 - Background: Cystic fibrosis (CF) patients would benefit from a safe and effective tool to detect early-stage, regional lung disease to allow for early intervention. Magnetic Resonance Imaging (MRI) is a safe, non-invasive procedure capable of providing quantitative assessments of disease without ionizing radiation. We developed a rapid normalized T1 MRI technique to detect regional lung disease in early-stage CF patients. Materials and Methods: Conventional multislice, pulmonary T1 relaxation time maps were obtained for 10 adult CF patients with normal spirometry and 5 healthy non-CF control subjects using a rapid Look-Locker MRI acquisition (5 seconds/imaging slice). Each lung absolute T1 map was separated into six regions of interest (ROI) by manually selecting upper, central, and lower lung regions in the left and right lungs. In order to reduce the effects of subject-to-subject variation, normalized T1 maps were calculated by dividing each pixel in the absolute T1 maps by the mean T1 time in the central lung region. The primary outcome was the differences in mean normalized T1 values in the upper lung regions between CF patients with normal spirometry and healthy volunteers. Results: Normalized T1 (nT1) maps showed visibly reduced subject-to-subject variation in comparison to conventional absolute T1 maps for healthy volunteers. An ROI analysis showed that the variation in the nT1 values in all regions was <= 2% of the mean. The primary outcome, the mean (SD) of the normalized T1 values in the upper right lung regions, was significantly lower in the CF subjects [.914 (.037)] compared to the upper right lung regions of the healthy subjects [.983 (.003)] [difference of .069 (95% confidence interval .032-.105); p=.001). Similar results were seen in the upper left lung region. Conclusion: Rapid normalized T1 MRI relaxometry obtained in 5 seconds/imaging slice may be used to detect regional early-stage lung disease in CF patients. KW - infants KW - disease KW - ventilation KW - infection KW - guidelines KW - diagnosis KW - children Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128346 SN - 1932-6203 VL - 8 IS - 9 ER - TY - JOUR A1 - Brumberg, Joachim A1 - Schröter, Nils A1 - Blazhenets, Ganna A1 - Frings, Lars A1 - Volkmann, Jens A1 - Lapa, Constantin A1 - Jost, Wolfgang H. A1 - Isaias, Ioannis U. A1 - Meyer, Philipp T. T1 - Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy JF - NPJ Parkinsons Disease N2 - [\(^{18}\)F]fluorodeoxyglucose (FDG) PET and [\(^{123}\)I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 +/- 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred. KW - clinical diagnosis KW - F-18-FDG PET KW - disease KW - dementia KW - accuracy KW - stimulation KW - guidelines KW - criteria KW - brain KW - risk Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230675 VL - 6 ER - TY - JOUR A1 - Borges, Alvaro H. A1 - O'Connor, Jemma L. A1 - Phillips, Andrew N. A1 - Baker, Jason V. A1 - Vjecha, Michael J. A1 - Losso, Marcelo H. A1 - Klinker, Hartwig A1 - Lopardo, Gustavo A1 - Williams, Ian A1 - Lundgren, Jens D. T1 - Factors Associated with D-Dimer Levels in HIV-Infected Individuals JF - PLOS ONE N2 - Background: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. Methods: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4(+) count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. Results: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. Conclusions: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels. KW - fibrin D-dimer KW - all-cause mortality KW - antiretroviral therapy KW - plasma D-dimer KW - elderly persons KW - coagulation KW - biomarkers KW - disease KW - interleukin-6 KW - adults Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117094 VL - 9 IS - 3 ER -