@article{BeckerRauSchmittetal.2015, author = {Becker, Philip P. and Rau, Monika and Schmitt, Johannes and Malsch, Carolin and Hammer, Christian and Bantel, Heike and M{\"u}llhaupt, Beat and Geier, Andreas}, title = {Performance of serum microRNAs -122, -192 and -21 as biomarkers in patients with non-alcoholic steatohepatitis}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0142661}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145147}, pages = {e0142661}, year = {2015}, abstract = {Objectives Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers. Methods Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH. Results The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95\% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91\%) and specificity (83\%). Conclusions Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.}, language = {en} } @article{MorbachWagnerGuentneretal.2017, author = {Morbach, Caroline and Wagner, Martin and G{\"u}ntner, Stefan and Malsch, Carolin and Oezkur, Mehmet and Wood, David and Kotseva, Kornelia and Leyh, Rainer and Ertl, Georg and Karmann, Wolfgang and Heuschmann, Peter U and St{\"o}rk, Stefan}, title = {Heart failure in patients with coronary heart disease: Prevalence, characteristics and guideline implementation - Results from the German EuroAspire IV cohort}, series = {BMC Cardiovascular Disorders}, volume = {17}, journal = {BMC Cardiovascular Disorders}, number = {108}, doi = {10.1186/s12872-017-0543-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157738}, year = {2017}, abstract = {Background: Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation. Methods: Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40\%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered. Results: 509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9\%), stage B in n = 264 (51.9\%), and stage C in n = 225 (44.2\%) patients; 94/225 patients were diagnosed with HFrEF (42\%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19\%). Overall GAI-3 of HFrEF patients was 96.4\% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription. Conclusions: In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists. Trial registration: This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.}, language = {en} } @article{MalschLimanWiedmannetal.2018, author = {Malsch, Carolin and Liman, Thomas and Wiedmann, Silke and Siegerink, Bob and Georgakis, Marios K. and Tiedt, Steffen and Endres, Matthias and Heuschmann, Peter U.}, title = {Outcome after stroke attributable to baseline factors—the PROSpective Cohort with Incident Stroke (PROSCIS)}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0204285}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177342}, pages = {e0204285}, year = {2018}, abstract = {Background The impact of risk factors on poor outcome after ischemic stroke is well known, but estimating the amount of poor outcome attributable to single factors is challenging in presence of multimorbidity. We aim to compare population attributable risk estimates obtained from different statistical approaches regarding their consistency. We use a real-life data set from the PROSCIS study to identify predictors for mortality and functional impairment one year after first-ever ischemic stroke and quantify their contribution to poor outcome using population attributable risks. Methods The PROSpective Cohort with Incident Stroke (PROSCIS) is a prospective observational hospital-based cohort study of patients after first-ever stroke conducted independently in Berlin (PROSCIS-B) and Munich (PROSCIS-M). The association of baseline factors with poor outcome one year after stroke in PROSCIS-B was analysed using multiple logistic regression analysis and population attributable risks were calculated, which were estimated using sequential population attributable risk based on a multiple generalized additive regression model, doubly robust estimation, as well as using average sequential population attributable risk. Findings were reproduced in an independent validation sample from PROSCIS-M. Results Out of 507 patients with available outcome information after 12 months in PROSCIS-B, 20.5\% suffered from poor outcome. Factors associated with poor outcome were age, pre-stroke physical disability, stroke severity (NIHSS), education, and diabetes mellitus. The order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but population attributable risk estimates varied markedly between the methods. In PROSCIS-M, incidence of poor outcome and distribution of baseline parameters were comparable. The multiple logistic regression model could be reproduced for all predictors, except pre-stroke physical disability. Similar to PROSCIS-B, the order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but magnitudes of population attributable risk differed markedly between the methods. Conclusions Ranking of risk factors by population impact is not affected by the different statistical approaches. Thus, for a rational decision on which risk factor to target in disease interventions, population attributable risk is a supportive tool. However, population attributable risk estimates are difficult to interpret and are not comparable when they origin from studies applying different methodology. The predictors for poor outcome identified in PROSCIS-B have a relevant impact on mortality and functional impairment one year after first-ever ischemic stroke.}, language = {en} } @article{MagyarWagnerThomasetal.2019, author = {Magyar, Attila and Wagner, Martin and Thomas, Phillip and Malsch, Carolin and Schneider, Reinhard and St{\"o}rk, Stefan and Heuschmann, Peter U and Leyh, Rainer G and Oezkur, Mehmet}, title = {HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study}, series = {International Journal of Nephrology and Renovascular Disease}, volume = {12}, journal = {International Journal of Nephrology and Renovascular Disease}, doi = {10.2147/IJNRD.S165308}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177250}, pages = {9-18}, year = {2019}, abstract = {Background: Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI. Patients and methods: In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated. Results: AKI with an incidence of 23.3\% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219). Conclusion: The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.}, language = {en} } @article{YurdadoganMalschKotsevaetal.2021, author = {Yurdadogan, Tino and Malsch, Carolin and Kotseva, Kornelia and Wood, David and Leyh, Rainer and Ertl, Georg and Karmann, Wolfgang and M{\"u}ller-Scholden, Lara and Morbach, Caroline and Breuning, Margret and Wagner, Martin and Gelbrich, G{\"o}tz and Bots, Michiel L. and Heuschmann, Peter U. and St{\"o}rk, Stefan}, title = {Functional versus morphological assessment of vascular age in patients with coronary heart disease}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-96998-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265810}, year = {2021}, abstract = {Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VA(PWVao) in 68\% of patients; for VA\(_{AIao}\) in 52\% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VA\(_{total-cIMT}\) accelerated vascular aging in 75\% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.}, language = {en} } @article{TuetuencueOlmaKunzeetal.2022, author = {T{\"u}t{\"u}nc{\"u}, Serdar and Olma, Manuel and Kunze, Claudia and Dietzel, Joanna and Schurig, Johannes and Fiessler, Cornelia and Malsch, Carolin and Haas, Tobias Eberhard and Dimitrijeski, Boris and Doehner, Wolfram and Hagemann, Georg and Hamilton, Frank and Honermann, Martin and Jungehulsing, Gerhard Jan and Kauert, Andreas and Koennecke, Hans-Christian and Mackert, Bruno-Marcel and Nabavi, Darius and Nolte, Christian H. and Reis, Joschua Mirko and Schmehl, Ingo and Sparenberg, Paul and Stingele, Robert and V{\"o}lzke, Enrico and Waldschmidt, Carolin and Zeise-Wehry, Daniel and Heuschmann, Peter U. and Endress, Matthias and Haeusler, Karl Georg}, title = {Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry}, series = {Journal of Neurology}, volume = {269}, journal = {Journal of Neurology}, number = {1}, issn = {1432-1459}, doi = {10.1007/s00415-021-10866-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266969}, pages = {470-480}, year = {2022}, abstract = {Aims We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. Methods The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. Results At stroke onset, an off-label daily dose was prescribed in 61 (25.5\%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8\%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95\% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95\% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2\%) of 61 patients. Overall, 79 (13.7\%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6\%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95\% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95\% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95\% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95\% CI 1.28-2.84, P < 0.01]. Conclusion At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge.}, language = {en} }