@article{SeydelmannLiuKraemeretal.2016,
  author    = {Seydelmann, Nora and Liu, Dan and Kr{\"a}mer, Johannes and Drechsler, Christiane and Hu, Kai and Nordbeck, Peter and Schneider, Andreas and St{\"o}rk, Stefan and Bijnens, Bart and Ertl, Georg and Wanner, Christoph and Weidemann, Frank},
  title     = {High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease},
  series = {Journal of the American Heart Association},
  volume    = {5},
  journal   = {Journal of the American Heart Association},
  number    = {e002839},
  doi       = {10.1161/JAHA.115.002839},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165682},
  year      = {2016},
  abstract  = {Background High-sensitivity troponin (hs-TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs-TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow-up study to assess longitudinal hs-TNT changes relative to fibrosis and cardiomyopathy progression. Methods and Results For the prospective analysis, hs-TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry-associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs-TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs-TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95\% CI, 3.56-302.59]; P=0.002); patients with elevated baseline hs-TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1-3.3] \%; follow-up, 3.2 [2.3-4.9] \%; P<0.001) and slightly elevated hs-TNT (baseline, 44.7 [30.1-65.3] ng/L; follow-up, 49.1 [27.6-69.5] ng/L; P=0.116) during follow-up. Left ventricular wall thickness and EF of patients with elevated hs-TNT were decreased during follow-up, indicating potential cardiomyopathy progression. Conclusions hs-TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs-TNT could be helpful for staging and follow-up of Fabry patients.},
  language  = {en}
}
@article{MitchellLiWeinholdetal.2016,
  author    = {Mitchell, Jonathan S. and Li, Ni and Weinhold, Niels and F{\"o}rsti, Asta and Ali, Mina and van Duin, Mark and Thorleifsson, Gudmar and Johnson, David C. and Chen, Bowang and Halvarsson, Britt-Marie and Gudbjartsson, Daniel F. and Kuiper, Rowan and Stephens, Owen W. and Bertsch, Uta and Broderick, Peter and Campo, Chiara and Einsele, Hermann and Gregory, Walter A. and Gullberg, Urban and Henrion, Marc and Hillengass, Jens and Hoffmann, Per and Jackson, Graham H. and Johnsson, Ellinor and J{\"o}ud, Magnus and Kristinsson, Sigurdur Y. and Lenhoff, Stig and Lenive, Oleg and Mellqvist, Ulf-Henrik and Migliorini, Gabriele and Nahi, Hareth and Nelander, Sven and Nickel, Jolanta and N{\"o}then, Markus M. and Rafnar, Thorunn and Ross, Fiona M. and da Silva Filho, Miguel Inacio and Swaminathan, Bhairavi and Thomsen, Hauke and Turesson, Ingemar and Vangsted, Annette and Vogel, Ulla and Waage, Anders and Walker, Brian A. and Wihlborg, Anna-Karin and Broyl, Annemiek and Davies, Faith E. and Thorsteinsdottir, Unnur and Langer, Christian and Hansson, Markus and Kaiser, Martin and Sonneveld, Pieter and Stefansson, Kari and Morgan, Gareth J. and Goldschmidt, Hartmut and Hemminki, Kari and Nilsson, Bj{\"o}rn and Houlston, Richard S.},
  title     = {Genome-wide association study identifies multiple susceptibility loci for multiple myeloma},
  series = {Nature Communications},
  volume    = {7},
  journal   = {Nature Communications},
  doi       = {10.1038/ncomms12050},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165983},
  pages     = {12050},
  year      = {2016},
  abstract  = {Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10-8), 6q21 (rs9372120, P=9.09 × 10-15), 7q36.1 (rs7781265, P=9.71 × 10-9), 8q24.21 (rs1948915, P=4.20 × 10-11), 9p21.3 (rs2811710, P=1.72 × 10-13), 10p12.1 (rs2790457, P=1.77 × 10-8), 16q23.1 (rs7193541, P=5.00 × 10-12) and 20q13.13 (rs6066835, P=1.36 × 10-13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.},
  language  = {en}
}
@article{BuschNadalSchmidetal.2016,
  author    = {Busch, Martin and Nadal, Jennifer and Schmid, Matthias and Paul, Katharina and Titze, Stephanie and H{\"u}bner, Silvia and K{\"o}ttgen, Anna and Schultheiss, Ulla T. and Baid-Agrawal, Seema and Lorenzen, Johan and Schlieper, Georg and Sommerer, Claudia and Krane, Vera and Hilge, Robert and Kielstein, Jan T. and Kronenberg, Florian and Wanner, Christoph and Eckardt, Kai-Uwe and Wolf, Gunter},
  title     = {Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort},
  series = {BMC Nephrology},
  volume    = {17},
  journal   = {BMC Nephrology},
  number    = {59},
  doi       = {10.1186/s12882-016-0273-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164687},
  year      = {2016},
  abstract  = {Background Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. Methods The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) between 30-60 mL/min/1.73 m2 or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. Results At baseline, DM was present in 1842 patients (35 \%) and the median HbA1C was 7.0 \% (25th-75th percentile: 6.8-7.9 \%), equalling 53 mmol/mol (51, 63); 24.2 \% of patients received dietary treatment only, 25.5 \% oral antidiabetic drugs but not insulin, 8.4 \% oral antidiabetic drugs with insulin, and 41.8 \% insulin alone. Metformin was used by 18.8 \%. Factors associated with an HbA1C level >7.0 \% (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m2, 95 \% CI 1.02-1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 \% CI 1.04-1.18), treatment with insulin alone (OR = 5.63, 95 \% CI 4.26-7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 \% CI 2.77-6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Conclusions Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 \% receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.},
  language  = {en}
}
@article{LiuHuNordbecketal.2016,
  author    = {Liu, Dan and Hu, Kai and Nordbeck, Peter and Ertl, Georg and St{\"o}rk, Stefan and Weidemann, Frank},
  title     = {Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy},
  series = {European Journal of Medical Research},
  volume    = {21},
  journal   = {European Journal of Medical Research},
  number    = {21},
  doi       = {10.1186/s40001-016-0216-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146373},
  year      = {2016},
  abstract  = {Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull's eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull's eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull's eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull's eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy.},
  language  = {en}
}
@article{DinnesBancosdiRuffanoetal.2016,
  author    = {Dinnes, Jacqueline and Bancos, Irina and di Ruffano, Lavinia Ferrante and Chortis, Vasileios and Davenport, Clare and Bayliss, Susan and Sahdev, Anju and Guest, Peter and Fassnacht, Martin and Deeks, Jonathan J and Arlt, Wiebke},
  title     = {Imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis},
  series = {European Journal of Endocrinology},
  volume    = {175},
  journal   = {European Journal of Endocrinology},
  number    = {2},
  doi       = {10.1530/EJE-16-0461},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188086},
  pages     = {R51-R64},
  year      = {2016},
  abstract  = {Objective: Adrenal masses are incidentally discovered in 5\% of CT scans. In 2013/2014, 81 million CT examinations were undertaken in the USA and 5 million in the UK. However, uncertainty remains around the optimal imaging approach for diagnosing malignancy. We aimed to review the evidence on the accuracy of imaging tests for differentiating malignant from benign adrenal masses. Design: A systematic review and meta-analysis was conducted. Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index, and ZETOC (January 1990 to August 2015). We included studies evaluating the accuracy of CT, MRI, or F-18-fluoro-deoxyglucose (FDG)-PET compared with an adequate histological or imaging-based follow-up reference standard. Results: We identified 37 studies suitable for inclusion, after screening 5469 references and 525 full-text articles. Studies evaluated the accuracy of CT (n = 16), MRI (n = 15), and FDG-PET (n = 9) and were generally small and at high or unclear risk of bias. Only 19 studies were eligible for meta-analysis. Limited data suggest that CT density >10 HU has high sensitivity for detection of adrenal malignancy in participants with no prior indication for adrenal imaging, that is, masses with <= 10 HU are unlikely to be malignant. All other estimates of test performance are based on too small numbers. Conclusions: Despite their widespread use in routine assessment, there is insufficient evidence for the diagnostic value of individual imaging tests in distinguishing benign from malignant adrenal masses. Future research is urgently needed and should include prospective test validation studies for imaging and novel diagnostic approaches alongside detailed health economics analysis.},
  language  = {en}
}
@article{PerkovicAgarwalFiorettoetal.2016,
  author    = {Perkovic, Vlado and Agarwal, Rajiv and Fioretto, Paola and Hemmelgarn, Brenda R. and Levin, Adeera and Thomas, Merlin C. and Wanner, Christoph and Kasiske, Bertram L. and Wheeler, David C. and Groop, Per-Henrik},
  title     = {Management of patients with diabetes and CKD: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) controversies conference},
  series = {Kidney International},
  volume    = {90},
  journal   = {Kidney International},
  number    = {6},
  doi       = {10.1016/j.kint.2016.09.010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186599},
  pages     = {1175-1183},
  year      = {2016},
  abstract  = {The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population.},
  language  = {en}
}
@article{OderVerghoErtletal.2016,
  author    = {Oder, Daniel and Vergho, Dorothee and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter},
  title     = {Case report of a 45-year old female Fabry disease patient carrying two alpha-galactosidase A gene mutation alleles},
  series = {BMC Medical Genetics},
  volume    = {17},
  journal   = {BMC Medical Genetics},
  number    = {46},
  doi       = {10.1186/s12881-016-0309-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146617},
  year      = {2016},
  abstract  = {Background X-chromosomal inheritance patterns and generally rare occurrence of Fabry disease (FD) account for mono-mutational hemizygous male and heterozygous female patients. Female mutation carriers are usually clinically much less severely affected, which has been explained by a suggested mosaicism in cell phenotype due to random allele shutdown. However, clinical evidence is scarce and potential additional effects in female gene carriers, which might account for specific clinical characteristics such as less severe chronic kidney disease, are yet unknown. Case presentation This article reports on a 45 year old female patient carrying the two alpha-galactosidase A gene mutations c.416A > G, p.N139S in exon 3 and c.708G > C, p.W236C in exon 5, but still showing only mild organ manifestations. Conclusion This current case highlights the importance of careful clinical characterization in patients with Fabry disease, who may show additional rare constellations and, therefore, are in need of personalized medicine. The impact of potential additional protective effects exceeding the presence of a non-pathogenic GLA allele in female gene carriers requires further investigation.},
  language  = {en}
}
@article{PetritschKoestlerWengetal.2016,
  author    = {Petritsch, B. and K{\"o}stler, H. and Weng, A. M. and Horn, M. and Gassenmaier, T. and Kunz, A. S. and Weidemann, F. and Wanner, C. and Bley, T. A. and Beer, M.},
  title     = {Myocardial lipid content in Fabry disease: a combined \(^1\)H-MR spectroscopy and MR imaging study at 3 Tesla},
  series = {BMC Cardiovascular Disorders},
  volume    = {16},
  journal   = {BMC Cardiovascular Disorders},
  number    = {205},
  doi       = {10.1186/s12872-016-0382-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146693},
  year      = {2016},
  abstract  = {Background Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by \(^1\)H magnetic resonance spectroscopy (MRS) at 3 Tesla. Methods Myocardial lipid content was quantified in vivo by \(^1\)H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined \(^1\)H-MRS with cardiac cine imaging and LGE MRI in a single examination. Results Myocardial lipid content was not significantly elevated in Fabry disease (p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI (LGE negative; n = 12) to patients with signs of fibrosis (LGE positive; n = 18) revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076). Conclusions This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by \(^1\)H-MRS. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections (LGE; \(^1\)H-MRS; T\(_1\) mapping), could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.},
  language  = {en}
}
@article{SbieraTryfonidouWeigandetal.2016,
  author    = {Sbiera, Silviu and Tryfonidou, Marianna A. and Weigand, Isabel and Grinwis, Guy C. M. and Broeckx, Bart and Herterich, Sabine and Allolio, Bruno and Deutschbein, Timo and Fassnacht, Martin and Meij, Bj{\"o}rn P.},
  title     = {Lack of Ubiquitin Specific Protease 8 (USP8) Mutations in Canine Corticotroph Pituitary Adenomas},
  series = {Plos One},
  volume    = {11},
  journal   = {Plos One},
  number    = {12},
  doi       = {10.1371/journal.pone.0169009},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148020},
  pages     = {e0169009},
  year      = {2016},
  abstract  = {Purpose Cushing's disease (CD), also known as pituitary-dependent hyperadrenocorticism, is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. Affected humans and dogs have similar clinical manifestations, however, the incidence of the canine disease is thousand-fold higher. This makes the dog an obvious model for studying the pathogenesis of pituitary-dependent hyperadrenocorticism. Despite certain similarities identified at the molecular level, the question still remains whether the two species have a shared oncogenetic background. Recently, hotspot recurrent mutations in the gene encoding for ubiquitin specific protease 8 (USP8) have been identified as the main driver behind the formation of ACTH-secreting pituitary adenomas in humans. In this study, we aimed to verify whether USP8 mutations also play a role in the development of such tumours in dogs. Methods Presence of USP8 mutations was analysed by Sanger and PCR-cloning sequencing in 38 canine ACTH-secreting adenomas. Furthermore, the role of USP8 and EGFR protein expression was assessed by immunohistochemistry in a subset of 25 adenomas. Results None of the analysed canine ACTH-secreting adenomas presented mutations in the USP8 gene. In a subset of these adenomas, however, we observed an increased nuclear expression of USP8, a phenotype characteristic for the USP8 mutated human tumours, that correlated with smaller tumour size but elevated ACTH production in those tumours. Conclusions Canine ACTH-secreting pituitary adenomas lack mutations in the USP8 gene suggesting a different genetic background of pituitary tumourigenesis in dogs. However, elevated nuclear USP8 protein expression in a subset of tumours was associated with a similar phenotype as in their human counterparts, indicating a possible end-point convergence of the different genetic backgrounds in the two species. In order to establish the dog as a useful animal model for the study of CD, further comprehensive studies are needed.},
  language  = {en}
}
@article{KirschmerBandleonvonEhrlichTreuenstaettetal.2016,
  author    = {Kirschmer, Nadine and Bandleon, Sandra and von Ehrlich-Treuenst{\"a}tt, Viktor and Hartmann, Sonja and Schaaf, Alice and Lamprecht, Anna-Karina and Miranda-Laferte, Erick and Langsenlehner, Tanja and Ritter, Oliver and Eder, Petra},
  title     = {TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0168446},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178539},
  year      = {2016},
  abstract  = {The Transient Receptor Potential Channel Subunit 4 (TRPC4) has been considered as a crucial Ca\(^{2+}\) component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na\(^{+}\) and Ca\(^{2+}\) influx. Gαq protein-coupled receptor (GPCR) stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca\(^{2+}\) influx which has been regarded as ideal Ca\(^{2+}\) source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT) activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4α and TRPC4β. Aim of the present study was to analyze cytosolic Ca\(^{2+}\) signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4α or TRPC4β. The analysis of Ca\(^{2+}\) transients in neonatal rat cardiomyocytes (NRCs) showed that TRPC4α and TRPC4β affected Ca\(^{2+}\) cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca\(^{2+}\) transient amplitude at baseline and TRPC4β increasing the Ca\(^{2+}\) peak during angiotensin II (Ang II) stimulation. NRCs infected with TRPC4β (Ad-C4β) also responded with a sustained Ca\(^{2+}\) influx when treated with Ang II under non-pacing conditions. Consistent with the Ca\(^{2+}\) data, NRCs infected with TRPC4α (Ad-C4α) showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4α reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4β NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not translated into an increased propensity towards hypertrophy but rather less hypertrophy during GPCR stimulation. Further analyses revealed that, although hypertrophy was preserved in Ad-C4α NRCs and even attenuated in Ad-C4β NRCs, cardiomyocytes had an increased apoptosis rate and thus were less viable after chronic GPCR stimulation. These findings suggest that TRPC4α and TRPC4β differentially affect Ca\(^{2+}\) signals, calcineurin/NFAT signaling and hypertrophy but similarly impair cardiomyocyte viability during GPCR stimulation.},
  language  = {en}
}
@article{LapaReiterKircheretal.2016,
  author    = {Lapa, Constantin and Reiter, Theresa and Kircher, Malte and Schirbel, Andreas and Werner, Rudolf A. and Pelzer, Theo and Pizarro, Carmen and Skowasch, Dirk and Thomas, Lena and Schlesinger-Irsch, Ulrike and Thomas, Daniel and Bundschuh, Ralph A. and Bauer, Wolfgang R. and Gartner, Florian C.},
  title     = {Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {47},
  doi       = {10.18632/oncotarget.12799},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175423},
  pages     = {77807-77814},
  year      = {2016},
  abstract  = {Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR-PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25\% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up. In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1\% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively. Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.},
  language  = {en}
}
@phdthesis{Spinnler2016,
  author    = {Spinnler, Christina},
  title     = {Prospektive Studie zum Auftreten von Nebennierenkrisen bei Patienten mit chronischer Nebenniereninsuffizienz},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140654},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Zusammenfassend ist die Inzidenz von NNK bei Patienten mit einer chronischen Nebennierenrindeninsuffizienz auch bei geschulten Patienten hoch. Das Auftreten der NNK ist zudem mit einer erheblichen Morbidit{\"a}t und Mortalit{\"a}t verkn{\"u}pft. In der heutigen Zeit sterben weiterhin Patienten an den Folgen ihrer chronischen NNRI trotz einer ad{\"a}quaten Behandlung. Legt man die oben genannten Zahlen zugrunde, werden in den n{\"a}chsten zehn Jahren zwischen 5526 und 10647 Patienten an einer behandelbaren NNK versterben. Dies macht die Notwendigkeit, die genauen Umst{\"a}nde und Ursachen einer NNK zu verstehen, noch wichtiger. Die Analysen der Risikofaktoren einer NNK haben jedoch nur ein begrenztes Potential, Patienten mit einem besonders hohen Risiko f{\"u}r das Auftreten von NKK zu identifizieren. Patientenaufkl{\"a}rungen im Hinblick auf Dosisanpassungen der Glukokortikoide in Stresssituationen werden die intraven{\"o}sen Gaben von Glukokortikoiden nicht unn{\"o}tig machen, um eine drohende NNK zu verhindern. Anstrengungen um eine einheitliche Patientenaufkl{\"a}rung mit dem Training der Selbstbehandlung mit parenteralem Hydrocortison werden essentiell sein, um die NNK als Todesursache zu verhindern. Die aktuelle Studie zeigt, dass die bisherigen Anstrengungen, eine einheitliche und breite Informationsgrundlage zu vermitteln, nicht ausreichend sind. Denn auch bei medizinischem Fachpersonal besteht anscheinend nach wie vor die Notwendigkeit einer intensiveren Schulung und Aufkl{\"a}rung. In mehreren telefonischen Kontakten berichteten Patienten, dass sich {\"a}rztliche Kollegen nur zur{\"u}ckhaltend auf eine ausreichend hohe intraven{\"o}se Cortisongabe einlassen konnten, in einem Fall sogar, obwohl der betroffene Patient einen Notfallausweis bei sich trug. Auch in der Laienpresse wurde von einem Fall berichtet, in dem laut Aussage der Patientin eine Cortisonanpassung nicht ausreichend erfolgte.[40] Da die meisten t{\"a}tigen {\"A}rzte nur sehr selten mit dem Krankheitsbild einer NNK konfrontiert sind, reagieren diese rezidivierend nicht ad{\"a}quat.[8] Auch zeigen sich die Symptome einer NNK h{\"a}ufig sehr unspezifisch, weshalb es vielen {\"A}rzten schwer fallen mag, diese zu erkennen. Da eine fr{\"u}hzeitige Intervention f{\"u}r ein gutes Out Come jedoch unverzichtbar ist, sollten weitere Anstrengungen gemacht werden, auch {\"a}rztliche Kollegen {\"u}ber diese Erkrankung und deren Behandlung aufzukl{\"a}ren. Weiterhin zeigt sich auch die Schulung von Familie und Freunden als sinnvoll, um das Aktionspotential im Falle einer akuten Verschlechterung der Nebennierenrindenerkrankung zu verst{\"a}rken. 423 Frageb{\"o}gen waren f{\"u}r die Ersterhebung verf{\"u}gbar, insgesamt schlossen 364 Patienten (84\%) das gesamte follow up {\"u}ber 2 Jahre ab. 767,5 Patientenjahre konnten {\"u}ber die Studie erfasst werden. Innerhalb der Erhebungszeit wurde von 64 NNK berichtet. Dies entspricht einer H{\"a}ufigkeit von 8,3 Krisen/100 Patientenjahre. Als Hauptausl{\"o}sefaktoren konnten gastrointestinale Infektionen, Fieber und emotionaler Stress erkannt werden. Die H{\"a}ufigkeit entsprach 20\%. Jedoch auch andere Stressoren konnten identifiziert werden. Hier zeigten sich zum Beispiel Operationen, starke Schmerzen, Hitze, anstrengende k{\"o}rperliche Bet{\"a}tigung und Schwangerschaft als urs{\"a}chlich. In 7\% der F{\"a}lle konnte bei einer pl{\"o}tzlichen Verschlechterung des Zustandes keine ausl{\"o}sende Ursache gefunden werden. Es fand sich jedoch, dass Patienten, die in ihrer Anamnese bereits eine oder mehrere NNK erlitten hatten, ein h{\"o}heres Risiko f{\"u}r eine erneute Entgleisung auswiesen. (Odds ratio 2,85, 95\% Konfidenzinterval 1.5-5.5, p 0,01) Andere Risikofaktoren konnten in der aktuellen Studie nicht identifiziert werden. W{\"a}hrend des Erhebungszeitraumes von zwei Jahren verstarben insgesamt zehn Patienten. Vier dieser Todesf{\"a}lle konnte einer NNK als Todesursache zugeordnet werden. Dies entspricht einer Mortalit{\"a}tsh{\"a}ufigkeit von 0,5/100 Patientenjahre. Somit war in unserer Studie die NNK-assoziierte Mortalit{\"a}t 6\% der NNK. Unsere Studienteilnehmer wurden zu Beginn des Follow ups detailliert {\"u}ber die Notwendigkeit von Dosisanpassungen und der Inanspruchnahme von professionellen Helfern aufgekl{\"a}rt. Dennoch zeigte sich im Vergleich zu anderen Studien mit 8,3 NNK/100 Patientenjahre keine reduzierte NNK-H{\"a}ufigkeit. Jedoch konnte durchaus eine Reduktion der NNK-H{\"a}ufigkeit im Vergleich zu den Daten im Ersterhebungsbogen gezeigt werden. Neben der Notwendigkeit, die Patientenaufkl{\"a}rung zu verbessern, zeigte die vorliegende Studie jedoch auch, dass weitere Anstrengungen gemacht werden m{\"u}ssen, um das Vorgehen vor und bei einer NNK weiterhin zu optimieren. So sind die genauen Umst{\"a}nde, die zu einer NNK f{\"u}hren, bis heute noch nicht detailliert gekl{\"a}rt. Zwar konnten einige Risikofaktoren und ausl{\"o}sende Situationen identifiziert werden, jedoch nicht die Frage, warum einige Patienten eine NNK bekommen und Andere nicht. In diesem Zusammenhang besteht auch weiterhin die Frage, warum einige Patienten gut auf eine Erh{\"o}hung der oralen Cortisondosis reagieren und Andere trotz der Erh{\"o}hung in eine NNK kommen. Hieraus ergibt sich die Frage, ob es Patienten gibt, die sensitiver auf das Cortison reagieren, und wenn dies der Fall ist, warum. Hierf{\"u}r k{\"o}nnte sprechen, dass es Patienten gibt, die rezidivierend in eine NNK kommen, w{\"a}hrend Andere nie ein Krise erleiden. Auch wird es weiterhin Anstrengungen und neue Strategien brauchen, eine schnellstm{\"o}gliche Intervention im Falle einer Verschlechterung des Allgemeinzustandes zu gew{\"a}hrleisten. Hier sind bessere, fl{\"a}chendeckende Aufkl{\"a}rungen f{\"u}r medizinisches Fachpersonal und/oder die Verbesserung der mitgef{\"u}hrten Notfallkarten notwendig. Eine Strategie, die Interventionszeit zu verk{\"u}rzen, w{\"a}re der Ausbau der Selbstinjektionen durch den betroffenen Patienten oder dessen Angeh{\"o}rige.},
  subject      = {Nebenniere},
  language  = {de}
}
@phdthesis{KrausertgebRiegel2016,
  author    = {Krausert [geb. Riegel], Katharina Margarete},
  title     = {Die klinsche Relevanz milder und moderater Hyponatri{\"a}mie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136185},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Ziel des Projektes war es, die klinische Beeintr{\"a}chtigung der chronisch mild und moderat hyponatri{\"a}men Patienten in einem longitudinalen Vergleich vor und nach Elektrolytkorrektur zu erfassen, um neue Therapieans{\"a}tze in der Behandlung der als asymptomatisch eingestuften Erkrankung zu erlangen. Die Studie unterteilte sich in einen diagnostischen Teil, in welchem Spontanurin und eine Blutprobe analysiert, sowie die klinische Anamnese erfasst wurden, und einen experimentellen Teil, in welchem eine kognitive und neuromuskul{\"a}re Testung erfolgte. Die kognitive Untersuchung erfasste die Reaktionsschnelligkeit und Konzentrationsf{\"a}higkeit der Patienten. Hierf{\"u}r standen die validierte Testbatterie zur Aufmerksamkeitspr{\"u}fung (TAP 2.0 f{\"u}r Windows) und das Softwarepaket Wiener Testsystem 32.0 zur Verf{\"u}gung. Die neuromuskul{\"a}re Testung erfolgte mit Hilfe der Messplattform Balance-X-Sensor. Das Vorgehen war standardisiert und reproduzierbar. Zus{\"a}tzlich wurde anhand eines Anamnesebogens die Auspr{\"a}gung klinischer Zeichen einer symptomatischen Hyponatri{\"a}mie erfragt (Kopfschmerzen, Konfusion, mentale Verlangsamung, Reizbarkeit, Streits{\"u}chtigkeit, Desorientierung zu Zeit/Ort/Person, M{\"u}digkeit, Leistungsf{\"a}higkeit, Schwindel, {\"U}belkeit, Erbrechen, Gangunsicherheit, St{\"u}rze, Kr{\"a}mpfe) und abschließend Daten {\"u}ber die aktuelle Lebensqualit{\"a}t der Patienten mit Hilfe des SF-36 Fragebogens erhoben. Im Anschluss an die Testungen wurden die Patienten dazu angewiesen, ihren Natriumhaushalt mithilfe einer individuellen Medikation, die unter Beachtung der aktuellen Behandlungsrichtlinien ausgew{\"a}hlt wurde, zu korrigieren. Eine Wiedervorstellung der Patienten erfolgte nach 14 Tagen um die Testungen im elektrolytkorrigierten Zustand zu wiederholen. Ein longitudinaler Vergleich der Messergebnisse soll Aufschluss {\"u}ber das Ausmaß einer Ver{\"a}nderung bez{\"u}glich der Leistungsf{\"a}higkeit und dem Empfinden der Patienten geben. Um den Querschnittsvergleich mit einem gesunden Kontrollkollektiv zu erm{\"o}glichen, fanden die neuromuskul{\"a}ren und kognitiven Testungen ebenfalls mit normonatri{\"a}men, gesunden Probanden statt. F{\"u}r den Querschnittsvergleich der Lebensqualit{\"a}tsmessung diente die international anerkannte US-Kontrollpopulation aus dem Jahr 1998. Die Studie wurde zur {\"u}bersichtlicheren Darstellung in zwei separate Arbeiten aufgeteilt. Der vorliegende Teil befasst sich mit der neuromuskul{\"a}ren Gleichgewichtstestung, sowie mit der Evaluierung der subjektiv empfundenen Lebensqualit{\"a}t der Patienten vor und nach Elektrolytkorrektur. Im Rahmen dieser Studie konnten Daten {\"u}ber das Gleichgewicht und die subjektive Lebensqualit{\"a}t von insgesamt 19 Patienten mit chronischer Hyponatri{\"a}mie (121-133 mmol/l) erhoben werden. Die Auswertung des Gleichgewichtstests mittels Balance-X-Sensor wies auf ein reduziertes Gleichgewichtsverm{\"o}gen der Patienten nach Elektrolytkorrektur hin. Hierbei konnte in keinem der ermittelten Parameter (Kraftvektorfl{\"a}che, Muskelleistungsfrequenz, Stehleistung) ein signifikanter Unterschied gezeigt werden. Vorangegangene Studien zum verbesserten Gleichgewichtsverm{\"o}gen nach medikament{\"o}ser Einstellung der Serumnatriumkonzentration konnten somit nicht best{\"a}tigt werden. Einzelne Steh{\"u}bungen wurden zudem von dem gesunden Kontrollkollektiv mit einem signifikant besseren Gleichgewicht, bei zugleich niedrigerer Standardabweichung, ausgef{\"u}hrt. Die Erfassung der Lebensqualit{\"a}t erfolgte mit Hilfe des SF-36 Fragebogens. Die Patienten wiesen nach Elektrolytkorrektur insgesamt keine signifikant verbesserte Lebensqualit{\"a}t auf. Im Querschnittsvergleich mit einer gesunden Kontrollpopulation wies die Auswertung der Frageb{\"o}gen auf eine insgesamt verminderte Lebensqualit{\"a}t, sowohl vor als auch nach Elektrolytkorrektur, hin. Die vorliegende Studie zeigt eine k{\"o}rperliche Beeintr{\"a}chtigung, sowie eine tendenziell verschlechterte subjektive Lebensqualit{\"a}t, chronisch mild hyponatri{\"a}mer Patienten. Eine signifikante Verbesserung der Werte konnte nach Anheben der Serumnatriumkonzentration nicht festgestellt werden. Die gewonnenen Ergebnisse sollten in Folgestudien mit einem gr{\"o}ßeren Patienten- und Probandenkollektiv, einem krankheitsspezifischen Fragebogen, sowie einem doppelblinden Studienaufbau {\"u}berpr{\"u}ft werden. Auch die M{\"o}glichkeit der Durchf{\"u}hrung einer multizentrischen Studie sollte gepr{\"u}ft werden. Der SF-36 Fragebogen und der Balance-X-Sensor k{\"o}nnen hierbei als kosteng{\"u}nstige Messinstrumente den subjektiven und objektiven Erfolg der Therapiemaßnahme dokumentieren. Ein konsequentes Anheben der Serumnatriumkonzentration bis in den Normbereich liefert zudem eine bessere Vergleichbarkeit mit internationalen Studien.},
  subject      = {Hyponatri{\"a}mie},
  language  = {de}
}
@phdthesis{Schober2016,
  author    = {Schober, Kilian},
  title     = {Der Einfluss von CLEC16A auf Autophagie - ein neuer Mechanismus in der Pathogenese von Typ-1-Diabetes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138715},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Das Gen CLEC16A ist mit der Autoimmunerkrankung Typ-1-Diabetes assoziiert. NOD-M{\"a}use mit einem Clec16a-KD sind vor der Entwicklung von Diabetes gesch{\"u}tzt, der entscheidende Wirkungsort f{\"u}r Clec16a sind dabei TECs. Im Rahmen zentraler Toleranz pr{\"a}sentieren TECs CD4+ Thymozyten Selbstantigene auf MHC II-Komplexen. Autophagie ist ein Zellprozess, der in TECs MHC II-Komplexen Selbstantigene zuf{\"u}hrt und so f{\"u}r die Entwicklung zentraler Toleranz essentiell ist. Das Ortholog von CLEC16A, ema, f{\"o}rdert die Bildung von Autophagosomen. So wurde vermutet, dass CLEC16A ein Suszeptibilit{\"a}tsgen f{\"u}r Typ-1-Diabetes ist, weil es Autophagie in TECs und somit deren MHC II-Beladung ver{\"a}ndert. Die vorliegende Arbeit schaltete CLEC16A in einer humanen Zelllinie durch RNAi aus und untersuchte die autophagische Aktivit{\"a}t dieser Zellen. Außerdem untersuchte sie die Autophagie von TECs aus NOD-Clec16a-KD-M{\"a}usen. Die Beurteilung erfolgte morphologisch durch Immunzytochemie bzw. -histochemie und funktionell durch Immunoblots. Es wurde gezeigt, dass der KD von CLEC16A in vitro und in vivo Autophagie funktionell beeintr{\"a}chtigt. Damit liefert die vorliegende Arbeit zusammen mit den Ergebnissen der Arbeitsgruppe Kissler einen m{\"o}glichen Erkl{\"a}rungsansatz, warum CLEC16A ein mit Typ-1-Diabetes assoziiertes Gen ist. CLEC16A f{\"o}rdert Autophagie in TECs, was die Selbstantigen-Beladung von MHC II-Komplexen ver{\"a}ndert. Selbstreaktive CD4+ Thymozyten f{\"u}hren so zum Verlust zentraler Toleranz und der Entwicklung von Typ-1-Diabetes. Weitere Untersuchungen sind jedoch notwendig, um diese Hypothese zu bekr{\"a}ftigen.},
  subject      = {Thymus},
  language  = {de}
}
@phdthesis{Lang2016,
  author    = {Lang, Mirjam},
  title     = {Diffusionsmessung mittels Rebreathing},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132750},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {F{\"u}r die Messung der Diffusionskapazit{\"a}t der Lunge f{\"u}r Kohlenmonoxid (Transferfak-tor) stehen verschiedene Verfahren zur Verf{\"u}gung. Die Messwerte f{\"u}r den Transferfak-tor unterscheiden sich nicht nur je nach dem angewandten Verfahren, sondern auch in Abh{\"a}ngigkeit von der technischen Ausr{\"u}stung und den Eigenheiten der Methodik. Ziel dieser Arbeit war es, ein neu eingef{\"u}hrtes Rebreath-Ger{\"a}t, das die Diffusionskapazit{\"a}t nach der von Stam (Stam et al. 1998) entwickelten Methode misst, in der klinischen Praxis zu testen. Die Messwerte sollten mit den Messungen nach dem Steady-State-Verfahren, das sich im Lungenfunktionslabor der Medizinischen Klinik und Poliklinik I der Universit{\"a}t W{\"u}rzburg bew{\"a}hrt hatte, in Beziehung gesetzt werden. Durch ad{\"a}quate Korrektur der Rebreath-Messwerte sollte eine m{\"o}glichst gute {\"U}bereinstimmung der kor-respondierenden Messwerte erzielt werden. Bei den untersuchten Patientenkollektiven handelte es sich um lungengesunde Proban-den und um Patienten mit obstruktiven bzw. restriktiven Lungenerkrankungen. Bei allen Kollektiven wurden Diffusionskapazit{\"a}tsmessungen nach beiden Verfahren durchge-f{\"u}hrt und parallel dazu auch spirometrische und bodyplethysmografische Untersuchun-gen vorgenommen. Die Auswertung der Messdaten umfasste zun{\"a}chst eine univariate Analyse zur Ermittlung von diagnostischen und demografischen Einflussgr{\"o}ßen (Pr{\"a}-diktoren) auf die Messwerte der beiden Verfahren und auf die Bodyplethysmographie. Anschließend wurden schrittweise mittels multipler linearer Regression aus den ver-schiedenen Einflussgr{\"o}ßen prim{\"a}re Pr{\"a}diktoren f{\"u}r die Messungen mit den beiden Ver-fahren ermittelt. Schließlich wurde eine Sch{\"a}tzformel abgeleitet, die unter der Ber{\"u}ck-sichtigung der wichtigsten Pr{\"a}diktoren die optimale N{\"a}herung der Rebreath-Messwerte an die korrespondierenden Steady-State-Messwerte erlaubte. Mit beiden Verfahren wurden f{\"u}r die Patienten niedrigere Werte der Diffusionskapazi-t{\"a}t ermittelt als f{\"u}r gesunde Probanden, mit den niedrigsten Werten bei Patienten mit restriktiver Lungenerkrankung. F{\"u}r obstruktiv Erkrankte fanden sich die h{\"o}chsten Alve-olarvolumina und entsprechend die niedrigsten Werte f{\"u}r den Krogh-Faktor. Mit beiden Verfahren konnte eine Abh{\"a}ngigkeit der Messwerte f{\"u}r den Transferfaktor von Ge-schlecht und Alter festgestellt werden. Als prim{\"a}rer Pr{\"a}diktor galt allerdings in beiden F{\"a}llen die Diagnose. Bemerkenswert ist der starke Einfluss des BMI auf einige der ge-messenen Parameter (TLCOkorr, Krogh-Faktor, DLCO\%), was eine st{\"a}rkere Ber{\"u}ck-sichtigung des BMI als pr{\"a}diktiven Faktor nahe legt. Die Korrelation zwischen den Messwerten aus den beiden Verfahren war m{\"a}ßig. Das Steady-State-Ger{\"a}t maß den Transferfaktor signifikant und wesentlich h{\"o}her als das Rebreath-Ger{\"a}t. Die schw{\"a}chste Korrelation fand sich unter allen untersuchten Parame-tern f{\"u}r die Prozentwerte vom Soll TLCO\% und DLCO\%. Die Abweichung der korres-pondierenden Messwerte unterschied sich zudem je nach Diagnose, Alter und H{\"o}he des Messwerts. Die Spirometrie und Bodyplethysmografie zeigte die zu erwartenden geschlechts-, al-ters- und diagnosespezifischen Charakteristika, wobei nahezu alle bodyplethysmografi-schen Parameter prim{\"a}r mit der Diagnose und nur sekund{\"a}r mit demografischen Fakto-ren korrelierten. Die Einsekundenkapazit{\"a}t FEV1 erwies sich als ein wichtiger Pr{\"a}diktor f{\"u}r die Steady-State-Diffusionskapazit{\"a}t und als geeignet, um die Rebreath-Messwerte der Zielsetzung entsprechend zu korrigieren. Sowohl f{\"u}r die Absolut- als auch f{\"u}r Rela-tivwerte der Diffusionskapazit{\"a}t konnte eine Sch{\"a}tzformel abgeleitet werden, welche die optimale N{\"a}herung der Rebreath-Werte an die entsprechenden Steady-State-Werte erm{\"o}glichte. Die bessere N{\"a}herung gelang f{\"u}r die Absolutwerte des Transferfaktors.},
  subject      = {Rebreathing},
  language  = {de}
}
@article{OderUeceylerLiuetal.2016,
  author    = {Oder, Daniel and {\"U}ceyler, Nurcan and Liu, Dan and Hu, Kai and Petritsch, Bernhard and Sommer, Claudia and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter},
  title     = {Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y},
  series = {BMJ Open},
  volume    = {6},
  journal   = {BMJ Open},
  doi       = {10.1136/bmjopen-2015-010422},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161210},
  pages     = {e010422},
  year      = {2016},
  abstract  = {Objectives: The severity of Fabry disease is dependent on the type of mutation in the α-galactosidase A (AgalA) encoding gene (GLA). This study focused on the impact of the GLA haplotype D313Y on long-term organ involvement and function. Setting and participants: In this monocentric study, all participants presenting with the D313Y haplotype between 2001 and 2015 were comprehensively clinically investigated at baseline and during a 4-year follow-up if available. Five females and one male were included. Primary and secondary outcome measures: Cardiac, nephrological, neurological, laboratory and quality of life data. Results: AgalA enzyme activity in leucocytes (0.3±0.9 nmol/min/mg protein (mean±SD)) and serum lyso-Gb3 (0.6±0.3 ng/mL at baseline) were in normal range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66±8\%; interventricular septum 7.7±1.4 mm; LV posterior wall 7.5±1.4 mm; normalised LV mass in MRI 52±9 g/m2; LV global longitudinal strain -21.6±1.9\%) and there were no signs of myocardial fibrosis in cardiac MRI. Cardiospecific biomarkers were also in normal range. Renal function was not impaired (estimated glomerular filtration rate MDRD 103±15 mL/min; serum-creatinine 0.75±0.07 mg/dL; cystatin-c 0.71±0.12 mg/L). One female patient (also carrying a Factor V Leiden mutation) had a transitory ischaemic attack. One patient showed white matter lesions in brain MRI, but none had Fabry-associated pain attacks, pain crises, evoked pain or permanent pain. Health-related quality of life analysis revealed a reduction in individual well-being. At long-term follow-up after 4 years, no significant change was seen in any parameter. Conclusions: The results of the current study suggest that the D313Y genotype does not lead to severe organ manifestations as seen in genotypes known to be causal for classical FD."},
  language  = {en}
}
@article{GratwohlPfirrmannZanderetal.2016,
  author    = {Gratwohl, A and Pfirrmann, M and Zander, A and Kr{\"o}ger, N and Beelen, D and Novotny, J and Nerl, C and Scheid, C and Spiekermann, K and Mayer, J and Sayer, HG and Falge, C and Bunjes, D and D{\"o}hner, H and Ganser, A and Schmidt-Wolf, I and Schwerdtfeger, R and Baurmann, H and Kuse, R and Schmitz, N and Wehmeier, A and Fischer, J Th and Ho, AD and Wilhelm, M and Goebeler, M-E and Lindemann, HW and Bormann, M and Hertenstein, B and Schlimok, G and Baerlocher, GM and Aul, C and Pfreundschuh, M and Fabian, M and Staib, P and Edinger, M and Schatz, M and Fauser, A and Arnold, R and Kindler, T and Wulf, G and Rosselet, A and Hellmann, A and Sch{\"a}fer, E and Pr{\"u}mmer, O and Schenk, M and Hasford, J and Heimpel, H and Hossfeld, DK and Kolb, H-J and B{\"u}sche, G and Haferlach, C and Schnittger, S and M{\"u}ller, MC and Reiter, A and Berger, U and Saußele, S and Hochhaus, A and Hehlmann, R},
  title     = {Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment},
  series = {Leukemia},
  volume    = {30},
  journal   = {Leukemia},
  doi       = {10.1038/leu.2015.281},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150368},
  pages     = {562-569},
  year      = {2016},
  abstract  = {Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95\% confidence interval (CI): 0.69-0.82) vs 0.69 (95\% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56\% vs 39\%; P = 0.005) and free of drug treatment (56\% vs 6\%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.},
  language  = {en}
}
@article{DuenasEspinVelaPauwsetal.2016,
  author    = {Due{\~n}as-Esp{\´i}n, Ivan and Vela, Emili and Pauws, Steffen and Bescos, Cristina and Cano, Isaac and Cleries, Montserrat and Contel, Joan Carles and Keenoy, Esteban de Manuel and Garcia-Aymerich, Judith and Gomez-Cabrero, David and Kaye, Rachelle and Lahr, Maarten M. H. and Lluch-Ariet, Mag{\´i} and Moharra, Montserrat and Monterde, David and Mora, Joana and Nalin, Marco and Pavlickova, Andrea and Piera, Jordi and Ponce, Sara and Santaeugenia, Sebasti{\`a} and Schonenberg, Helen and St{\"o}rk, Stefan and Tegner, Jesper and Velickovski, Filip and Westerteicher, Christoph and Roca, Josep},
  title     = {Proposals for enhanced health risk assessment and stratification in an integrated care scenario},
  series = {BMJ Open},
  volume    = {6},
  journal   = {BMJ Open},
  number    = {e010301},
  doi       = {10.1136/bmjopen-2015-010301},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164743},
  year      = {2016},
  abstract  = {Objectives Population-based health risk assessment and stratification are considered highly relevant for large-scale implementation of integrated care by facilitating services design and case identification. The principal objective of the study was to analyse five health-risk assessment strategies and health indicators used in the five regions participating in the Advancing Care Coordination and Telehealth Deployment (ACT) programme (http://www.act-programme.eu). The second purpose was to elaborate on strategies toward enhanced health risk predictive modelling in the clinical scenario. Settings The five ACT regions: Scotland (UK), Basque Country (ES), Catalonia (ES), Lombardy (I) and Groningen (NL). Participants Responsible teams for regional data management in the five ACT regions. Primary and secondary outcome measures We characterised and compared risk assessment strategies among ACT regions by analysing operational health risk predictive modelling tools for population-based stratification, as well as available health indicators at regional level. The analysis of the risk assessment tool deployed in Catalonia in 2015 (GMAs, Adjusted Morbidity Groups) was used as a basis to propose how population-based analytics could contribute to clinical risk prediction. Results There was consensus on the need for a population health approach to generate health risk predictive modelling. However, this strategy was fully in place only in two ACT regions: Basque Country and Catalonia. We found marked differences among regions in health risk predictive modelling tools and health indicators, and identified key factors constraining their comparability. The research proposes means to overcome current limitations and the use of population-based health risk prediction for enhanced clinical risk assessment. Conclusions The results indicate the need for further efforts to improve both comparability and flexibility of current population-based health risk predictive modelling approaches. Applicability and impact of the proposals for enhanced clinical risk assessment require prospective evaluation.},
  language  = {en}
}
@article{DienemannFujiiOrlandietal.2016,
  author    = {Dienemann, Thomas and Fujii, Naohiko and Orlandi, Paula and Nessel, Lisa and Furth, Susan L. and Hoy, Wendy E. and Matsuo, Seiichi and Mayer, Gert and Methven, Shona and Schaefer, Franz and Schaeffner, Elke S. and Sol{\´a}, Laura and Stengel, B{\´e}n{\´e}dicte and Wanner, Christoph and Zhang, Luxia and Levin, Adeera and Eckardt, Kai-Uwe and Feldman, Harold I.},
  title     = {International Network of Chronic Kidney Disease cohort studies (iNET-CKD): a global network of chronic kidney disease cohorts},
  series = {BMC Nephrology},
  volume    = {17},
  journal   = {BMC Nephrology},
  doi       = {10.1186/s12882-016-0335-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164604},
  pages     = {121},
  year      = {2016},
  abstract  = {Background Chronic kidney disease (CKD) is a global health burden, yet it is still underrepresented within public health agendas in many countries. Studies focusing on the natural history of CKD are challenging to design and conduct, because of the long time-course of disease progression, a wide variation in etiologies, and a large amount of clinical variability among individuals with CKD. With the difference in health-related behaviors, healthcare delivery, genetics, and environmental exposures, this variability is greater across countries than within one locale and may not be captured effectively in a single study. Methods Studies were invited to join the network. Prerequisites for membership included: 1) observational designs with a priori hypotheses and defined study objectives, patient-level information, prospective data acquisition and collection of bio-samples, all focused on predialysis CKD patients; 2) target sample sizes of 1,000 patients for adult cohorts and 300 for pediatric cohorts; and 3) minimum follow-up of three years. Participating studies were surveyed regarding design, data, and biosample resources. Results Twelve prospective cohort studies and two registries covering 21 countries were included. Participants age ranges from >2 to >70 years at inclusion, CKD severity ranges from stage 2 to stage 5. Patient data and biosamples (not available in the registry studies) are measured yearly or biennially. Many studies included multiple ethnicities; cohort size ranges from 400 to more than 13,000 participants. Studies' areas of emphasis all include but are not limited to renal outcomes, such as progression to ESRD and death. Conclusions iNET-CKD (International Network of CKD cohort studies) was established, to promote collaborative research, foster exchange of expertise, and create opportunities for research training. Participating studies have many commonalities that will facilitate comparative research; however, we also observed substantial differences. The diversity we observed across studies within this network will be able to be leveraged to identify genetic, behavioral, and health services factors associated with the course of CKD. With an emerging infrastructure to facilitate interactions among the investigators of iNET-CKD and a broadly defined research agenda, we are confident that there will be great opportunity for productive collaborative investigations involving cohorts of individuals with CKD.},
  language  = {en}
}
@article{UeceylerSchroeterKafkeetal.2016,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Schr{\"o}ter, Nils and Kafke, Waldemar and Kramer, Daniela and Wanner, Christoph and Weidemann, Frank and Sommer, Claudia},
  title     = {Skin Globotriaosylceramide 3 Load Is Increased in Men with Advanced Fabry Disease},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {11},
  doi       = {10.1371/journal.pone.0166484},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178856},
  year      = {2016},
  abstract  = {Background The X-chromosomally linked life-limiting Fabry disease (FD) is associated with deposits of the sphingolipid globotriaosylceramide 3 (Gb3) in various tissues. Skin is easily accessible and may be used as an additional diagnostic and follow-up medium. Our aims were to visualize skin Gb3 deposits in FD patients applying immunofluorescence and to determine if cutaneous Gb3 load correlates with disease severity. Methods At our Fabry Center for Interdisciplinary Therapy we enrolled 84 patients with FD and 27 healthy controls. All subjects underwent 5-mm skin punch biopsy at the lateral lower leg and the back. Skin samples were processed for immunohistochemistry using antibodies against CD77 (i.e. Gb3). Cutaneous Gb3 deposition was quantified in a blinded manner and correlated to clinical data. Results We found that Gb3 load was higher in distal skin of male FD patients compared to healthy controls (p<0.05). Men (p<0.01) and women (p<0.05) with a classic FD phenotype had higher distal skin Gb3 load than healthy controls. Men with advanced disease as reflected by impaired renal function, and men and women with small fiber neuropathy had more Gb3 deposits in distal skin samples than males with normal renal function (p<0.05) and without small fiber neuropathy. Gb3 deposits were not different between patients with and without enzyme replacement therapy. Conclusions Immunofluorescence on minimally invasive skin punch biopsies may be useful as a tool for assessment and follow-up in FD patients.},
  language  = {en}
}