@article{AltieriSbieraHerterichetal.2020,
  author    = {Altieri, Barbara and Sbiera, Silviu and Herterich, Sabine and De Francia, Silvia and Della Casa, Silvia and Calabrese, Anna and Pontecorvi, Alfredo and Quinkler, Marcus and Kienitz, Tina and Mannelli, Massimo and Canu, Letizia and Angelousi, Anna and Chortis, Vasileios and Kroiss, Matthias and Terzolo, Massimo and Fassnacht, Martin and Ronchi, Cristina L.},
  title     = {Effects of Germline CYP2W1*6 and CYP2B6*6 Single Nucleotide Polymorphisms on Mitotane Treatment in Adrenocortical Carcinoma: A Multicenter ENSAT Study},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {2},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12020359},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200565},
  pages     = {359},
  year      = {2020},
  abstract  = {Mitotane is the only approved drug for advanced adrenocortical carcinoma (ACC) and no biomarkers are available to predict attainment of therapeutic plasma concentrations and clinical response. Aim of the study was to evaluate the suitability of cytochrome P450(CYP)2W1 and CYP2B6 single nucleotide polymorphisms (SNPs) as biomarkers. A multicenter cohort study including 182 ACC patients (F/M = 121/61) treated with mitotane monotherapy after radical resection (group A, n = 103) or in not completely resectable, recurrent or advanced disease (group B, n = 79) was performed. CYP2W1*2, CYP2W1*6, CYP2B6*6 and CYP2B6 rs4803419 were genotyped in germline DNA. Mitotane blood levels were measured regularly. Response to therapy was evaluated as time to progression (TTP) and disease control rate (DCR). Among investigated SNPs, CYP2W1*6 and CYP2B6*6 correlated with mitotane treatment only in group B. Patients with CYP2W1*6 (n = 21) achieved less frequently therapeutic mitotane levels (>14 mg/L) than those with wild type (WT) allele (76.2\% vs 51.7\%, p = 0.051) and experienced shorter TTP (HR = 2.10, p = 0.019) and lower DCR (chi-square = 6.948, p = 0.008). By contrast, 55\% of patients with CYP2B6*6 vs. 28.2\% WT (p = 0.016) achieved therapeutic range. Combined, a higher rate of patients with CYP2W1*6WT+CYP2B6*6 (60.6\%) achieved mitotane therapeutic range (p = 0.034). In not completely resectable, recurrent or advanced ACC, CYP2W1*6 SNP was associated with a reduced probability to reach mitotane therapeutic range and lower response rates, whereas CYP2B6*6 correlated with higher mitotane levels. The association of these SNPs may predict individual response to mitotane.},
  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{OrtizAbioseBichetetal.2016,
  author    = {Ortiz, Alberto and Abiose, Ademola and Bichet, Daniel G. and Cabrera, Gustavo and Charrow, Joel and Germain, Dominique P. and Hopkin, Robert J. and Jovanovic, Ana and Linhart, Aleš and Maruti, Sonia S. and Mauer, Michael and Oliveira, Jo{\~a}o P. and Patel, Manesh R. and Politei, Juan and Waldek, Stephen and Wanner, Christoph and Yoo, Han-Wook and Warnock, David G.},
  title     = {Time to treatment benefit for adult patients with Fabry disease receiving agalsidase beta: data from the Fabry Registry},
  series = {Journal of Medical Genetics},
  volume    = {53},
  journal   = {Journal of Medical Genetics},
  number    = {7},
  doi       = {10.1136/jmedgenet-2015-103486},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188241},
  pages     = {495-502},
  year      = {2016},
  abstract  = {Background Agalsidase beta is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low alpha-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase beta cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase beta treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase beta. Methods The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase beta (average dose 1 mg/kg every 2 weeks) for up to 5 years. Results The incidence of all severe clinical events was 111 per 1000 person-years (95\% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged >= 40 years when agalsidase beta was initiated. Conclusions Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase beta 1 mg/kg every 2 weeks.},
  language  = {en}
}
@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{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{DietrichKrebsLimanetal.2019,
  author    = {Dietrich, Georg and Krebs, Jonathan and Liman, Leon and Fette, Georg and Ertl, Maximilian and Kaspar, Mathias and St{\"o}rk, Stefan and Puppe, Frank},
  title     = {Replicating medication trend studies using ad hoc information extraction in a clinical data warehouse},
  series = {BMC Medical Informatics and Decision Making},
  volume    = {19},
  journal   = {BMC Medical Informatics and Decision Making},
  doi       = {10.1186/s12911-018-0729-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200409},
  pages     = {15},
  year      = {2019},
  abstract  = {Background Medication trend studies show the changes of medication over the years and may be replicated using a clinical Data Warehouse (CDW). Even nowadays, a lot of the patient information, like medication data, in the EHR is stored in the format of free text. As the conventional approach of information extraction (IE) demands a high developmental effort, we used ad hoc IE instead. This technique queries information and extracts it on the fly from texts contained in the CDW. Methods We present a generalizable approach of ad hoc IE for pharmacotherapy (medications and their daily dosage) presented in hospital discharge letters. We added import and query features to the CDW system, like error tolerant queries to deal with misspellings and proximity search for the extraction of the daily dosage. During the data integration process in the CDW, negated, historical and non-patient context data are filtered. For the replication studies, we used a drug list grouped by ATC (Anatomical Therapeutic Chemical Classification System) codes as input for queries to the CDW. Results We achieve an F1 score of 0.983 (precision 0.997, recall 0.970) for extracting medication from discharge letters and an F1 score of 0.974 (precision 0.977, recall 0.972) for extracting the dosage. We replicated three published medical trend studies for hypertension, atrial fibrillation and chronic kidney disease. Overall, 93\% of the main findings could be replicated, 68\% of sub-findings, and 75\% of all findings. One study could be completely replicated with all main and sub-findings. Conclusion A novel approach for ad hoc IE is presented. It is very suitable for basic medical texts like discharge letters and finding reports. Ad hoc IE is by definition more limited than conventional IE and does not claim to replace it, but it substantially exceeds the search capabilities of many CDWs and it is convenient to conduct replication studies fast and with high quality.},
  language  = {en}
}
@article{ManiucSalingerAndersetal.2019,
  author    = {Maniuc, Octavian and Salinger, Tim and Anders, Fabian and M{\"u}ntze, Jonas and Liu, Dan and Hu, Kai and Ertl, Georg and Frantz, Stefan and Nordbeck, Peter},
  title     = {Impella CP use in patients with non-ischaemic cardiogenic shock},
  series = {ESC Heart Failure},
  volume    = {6},
  journal   = {ESC Heart Failure},
  number    = {4},
  doi       = {10.1002/ehf2.12446},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202794},
  pages     = {863- 866},
  year      = {2019},
  abstract  = {Aims From the various mechanical cardiac assist devices and indications available, the use of the percutaneous intraventricular Impella CP pump is usually restricted to acute ischaemic shock or prophylactic indications in high-risk interventions. In the present study, we investigated clinical usefulness of the Impella CP device in patients with non-ischaemic cardiogenic shock as compared with acute ischaemia. Methods and results In this retrospective single-centre analysis, patients who received an Impella CP at the University Hospital W{\"u}rzburg between 2013 and 2017 due to non-ischaemic cardiogenic shock were age-matched 2:1 with patients receiving the device due to ischaemic cardiogenic shock. Inclusion criteria were therapy refractory haemodynamic instability with severe left ventricular systolic dysfunction and serum lactate >2.0 mmol/L at implantation. Basic clinical data, indications for mechanical ventricular support, and outcome were obtained in all patients with non-ischaemic as well as ischaemic shock and compared between both groups. Continuous variables are expressed as mean ± standard deviation or median (quartiles). Categorical variables are presented as count and per cent. Twenty-five patients had cardiogenic shock due to non-ischaemic reasons and were compared with 50 patients with cardiogenic shock due to acute myocardial infarction. Resuscitation rates before implantation of Impella CP were high (32 vs. 42\%; P = 0.402). At implantation, patients with non-ischaemic cardiogenic shock had lower levels of high-sensitive troponin T (110.65 [57.87-322.1] vs. 1610 [450.8-3861.5] pg/mL; P = 0.001) and lactate dehydrogenase (377 [279-608] vs. 616 [371.3-1109] U/L; P = 0.007), while age (59 ± 16 vs. 61.7 ± 11; P = 0.401), glomerular filtration rate (43.5 [33.2-59.7] vs. 48 [35.75-69] mL/min; P = 0.290), C-reactive protein (5.17 [3.27-10.26] vs. 10.97 [3.23-17.2] mg/dL; P = 0.195), catecholamine index (30.6 [10.6-116.9] vs. 47.6 [11.7-90] μg/kg/min; P = 0.663), and serum lactate (2.6 [2.2-5.8] vs. 2.9 [1.3-6.6] mmol/L; P = 0.424) were comparable between both groups. There was a trend for longer duration of Impella support in the non-ischaemic groups (5 [2-7.5] vs. 3 [2-5.25] days, P = 0.211). Rates of haemodialysis (52 vs. 47\%; P = 0.680) and transition to extracorporeal membrane oxygenation (13.6 vs. 22.2\%; P = 0.521) were comparable. No significant difference was found regarding both 30 day survival (48 vs. 30\%; P = 0.126) and in-hospital mortality (66.7 vs. 74\%; P = 0.512), although there was a trend for better survival in the non-ischaemic group. Conclusions These data suggest that temporary use of the Impella CP device might be a useful therapeutic option for bridge to recovery not only in ischaemic but also in non-ischaemic cardiogenic shock.},
  language  = {en}
}
@article{MuellerScholdenKirchhofMorbachetal.2019,
  author    = {M{\"u}ller-Scholden, Lara and Kirchhof, Jan and Morbach, Caroline and Breunig, Margret and Meijer, Rudy and R{\"u}cker, Viktoria and Tiffe, Theresa and Yurdadogan, Tino and Wagner, Martin and Gelbrich, G{\"o}tz and Bots, Michiel L. and St{\"o}rk, Stefan and Heuschmann, Peter U.},
  title     = {Segment-specific association of carotid-intima-media thickness with cardiovascular risk factors - findings from the STAAB cohort study},
  series = {BMC Cardiovascular Disorders},
  volume    = {19},
  journal   = {BMC Cardiovascular Disorders},
  number    = {84},
  doi       = {10.1186/s12872-019-1044-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200720},
  year      = {2019},
  abstract  = {Background The guideline recommendation to not measure carotid intima-media thickness (CIMT) for cardiovascular risk prediction is based on the assessment of just one single carotid segment. We evaluated whether there is a segment-specific association between different measurement locations of CIMT and cardiovascular risk factors. Methods Subjects from the population-based STAAB cohort study comprising subjects aged 30 to 79 years of the general population from W{\"u}rzburg, Germany, were investigated. CIMT was measured on the far wall of both sides in three different predefined locations: common carotid artery (CCA), bulb, and internal carotid artery (ICA). Diabetes, dyslipidemia, hypertension, smoking, and obesity were considered as risk factors. In multivariable logistic regression analysis, odds ratios of risk factors per location were estimated for the endpoint of individual age- and sex-adjusted 75th percentile of CIMT. Results 2492 subjects were included in the analysis. Segment-specific CIMT was highest in the bulb, followed by CCA, and lowest in the ICA. Dyslipidemia, hypertension, and smoking were associated with CIMT, but not diabetes and obesity. We observed no relevant segment-specific association between the three different locations and risk factors, except for a possible interaction between smoking and ICA. Conclusions As no segment-specific association between cardiovascular risk factors and CIMT became evident, one simple measurement of one location may suffice to assess the cardiovascular risk of an individual.},
  language  = {en}
}
@article{HeidenreichWengDonhauseretal.2019,
  author    = {Heidenreich, Julius F. and Weng, Andreas M. and Donhauser, Julian and Greiser, Andreas and Chow, Kelvin and Nordbeck, Peter and Bley, Thorsten A. and K{\"o}stler, Herbert},
  title     = {T1- and ECV-mapping in clinical routine at 3 T: differences between MOLLI, ShMOLLI and SASHA},
  series = {BMC Medical Imaging},
  volume    = {19},
  journal   = {BMC Medical Imaging},
  doi       = {10.1186/s12880-019-0362-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201999},
  pages     = {59},
  year      = {2019},
  abstract  = {Background T1 mapping sequences such as MOLLI, ShMOLLI and SASHA make use of different technical approaches, bearing strengths and weaknesses. It is well known that obtained T1 relaxation times differ between the sequence techniques as well as between different hardware. Yet, T1 quantification is a promising tool for myocardial tissue characterization, disregarding the absence of established reference values. The purpose of this study was to evaluate the feasibility of native and post-contrast T1 mapping methods as well as ECV maps and its diagnostic benefits in a clinical environment when scanning patients with various cardiac diseases at 3 T. Methods Native and post-contrast T1 mapping data acquired on a 3 T full-body scanner using the three pulse sequences 5(3)3 MOLLI, ShMOLLI and SASHA in 19 patients with clinical indication for contrast enhanced MRI were compared. We analyzed global and segmental T1 relaxation times as well as respective extracellular volumes and compared the emerged differences between the used pulse sequences. Results T1 times acquired with MOLLI and ShMOLLI exhibited systematic T1 deviation compared to SASHA. Myocardial MOLLI T1 times were 19\% lower and ShMOLLI T1 times 25\% lower compared to SASHA. Native blood T1 times from MOLLI were 13\% lower than SASHA, while post-contrast MOLLI T1-times were only 5\% lower. ECV values exhibited comparably biased estimation with MOLLI and ShMOLLI compared to SASHA in good agreement with results reported in literature. Pathology-suspect segments were clearly differentiated from remote myocardium with all three sequences. Conclusion Myocardial T1 mapping yields systematically biased pre- and post-contrast T1 times depending on the applied pulse sequence. Additionally calculating ECV attenuates this bias, making MOLLI, ShMOLLI and SASHA better comparable. Therefore, myocardial T1 mapping is a powerful clinical tool for classification of soft tissue abnormalities in spite of the absence of established reference values.},
  language  = {en}
}
@article{HaringCrandallCarboneetal.2019,
  author    = {Haring, Bernhard and Crandall, Carolyn J and Carbone, Laura and Liu, Simin and Li, Wenjun and Johnson, Karen C and Wactawski-Wende, Jean and Shadyab, Aladdin H and Gass, Margery L and Kamensky, Victor and Cauley, Jane A and Wassertheil-Smoller, Sylvia},
  title     = {Lipoprotein(a) plasma levels, bone mineral density and risk of hip fracture: a post hoc analysis of the Women's Health Initiative, USA},
  series = {BMJ Open},
  volume    = {9},
  journal   = {BMJ Open},
  doi       = {10.1136/bmjopen-2018-027257},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201139},
  pages     = {e027257},
  year      = {2019},
  abstract  = {Objectives Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women. Design Post hoc analysis of data from the Women's Health Initiative (WHI), USA. Setting 40 clinical centres in the USA. Participants The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast and colorectal cancers and osteoporotic fractures among postmenopausal women. Recruitment for WHI took place from 1 October 1993 to 31 December 1998. Exposures Plasma Lp(a) levels were measured at baseline. Outcome measures Incident hip fractures were ascertained annually and confirmed by medical records with follow-up through 29 August 2014. BMD at the femoral neck was measured by dual X-ray absorptiometry in a subset of participants at baseline. Statistical analyses Cox proportional hazards and logistic regression models were used to evaluate associations of quartiles of plasma Lp(a) levels with hip fracture events and hip BMD T-score, respectively. Results During a mean follow-up of 13.8 years, 454 incident cases of hip fracture were observed. In analyses adjusting for confounding variables including age, body mass index, history of hysterectomy, smoking, physical activity, diabetes mellitus, general health status, cardiovascular disease, use of menopausal hormone therapy, use of bisphosphonates, calcitonin or selective-oestrogen receptor modulators, baseline dietary and supplemental calcium and vitamin D intake and history of fracture, no significant association of plasma Lp(a) levels with low hip BMD T-score or hip fracture risk was detected. Conclusions These findings suggest that plasma Lp(a) levels are not related to hip BMD T-score or hip fracture events in postmenopausal women.},
  language  = {en}
}