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Carolin Malsch

Bio: Carolin Malsch is an academic researcher from University of Würzburg. The author has contributed to research in topics: Stroke & Population. The author has an hindex of 9, co-authored 18 publications receiving 391 citations. Previous affiliations of Carolin Malsch include Greifswald University Hospital & University of Greifswald.

Papers
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Journal ArticleDOI
TL;DR: It is emphasized that circulating miRNAs are strongly impacted by age, BMI, and sex, and these parameters should be considered as covariates in association studies based on plasma miRNA levels.
Abstract: Non-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP). Quantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest. After regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters. These findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.

136 citations

Journal ArticleDOI
TL;DR: It is demonstrated that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia.
Abstract: Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests...

118 citations

Journal ArticleDOI
13 Nov 2015-PLOS ONE
TL;DR: Candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH are defined.
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.

109 citations

Journal ArticleDOI
TL;DR: The degree of MTA was strongly associated with the severity of cognitive impairment, whereas the extent of white matter hyperintensities was similar in patients and controls and patients had a 2.7-fold increased risk for presence of clinically silent lacunes.
Abstract: Objectives This study sought to determine the spectrum of brain lesions seen in heart failure (HF) patients and the extent to which lesion type contributes to cognitive impairment. Background Cognitive deficits have been reported in patients with HF. Methods A total of 148 systolic and diastolic HF patients (mean age 64 ± 11 years; 16% female; mean left ventricular ejection fraction 43 ± 8%) were extensively evaluated within 2 days by cardiological, neurological, and neuropsychological testing and brain magnetic resonance imaging (MRI). A total of 288 healthy, sex- and age-matched subjects sampled from the Austrian Stroke Prevention Study served as MRI controls. Results Deficits in reaction times were apparent in 41% of patients and deficits in verbal memory in 46%. On brain MRI, patients showed more advanced medial temporal lobe atrophy (MTA) (Scheltens score) compared to controls (2.1 ± 0.9 vs. 1.0 ± 0.6; p Conclusions HF patients exhibit cognitive deficits in the domains of attention and memory. MTA but not white matter lesion load seems to be related to cognitive impairment.

64 citations

Journal ArticleDOI
TL;DR: In this article, the effect of systematic electrocardiogram (ECG) monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months was assessed.
Abstract: Summary Background Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. Methods In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov , NCT02204267 , and is completed and closed for participants. Findings Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9–1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0–2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 vs 249 [14·5%] of 1717; HR 0·9 [0·8–1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5–0·9]). Interpretation Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. Funding Bayer Vital. Translation For the German translation of the abstract see Supplementary Materials section.

48 citations


Cited by
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01 Dec 2019-Stroke
TL;DR: These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks.
Abstract: Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

3,819 citations

Journal ArticleDOI
TL;DR: Whether therapies to modulate inflammageing can reduce the age-related decline in health is discussed, and the hypothesis that inflammation affects CVD, multimorbidity, and frailty is supported by mechanistic studies but requires confirmation in humans.
Abstract: Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty — which affect clinical manifestations, prognosis, and response to treatment — and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials. Inflammageing is a chronic, pro-inflammatory state that develops with age and is a risk factor for cardiovascular disease, comorbidities, frailty, and death. In this Review, Ferrucci and Fabbri discuss whether therapies to modulate inflammageing can reduce the age-related decline in health.

1,428 citations

Journal ArticleDOI
Jonas Schulte-Schrepping1, Nico Reusch1, Daniela Paclik2, Kevin Baßler1, Stephan Schlickeiser2, Bowen Zhang3, Benjamin Krämer4, Tobias Krammer, Sophia Brumhard2, Lorenzo Bonaguro1, Elena De Domenico5, Daniel Wendisch2, Martin Grasshoff3, Theodore S. Kapellos1, Michael Beckstette3, Tal Pecht1, Adem Saglam5, Oliver Dietrich, Henrik E. Mei6, Axel Schulz6, Claudia Conrad2, Désirée Kunkel2, Ehsan Vafadarnejad, Cheng-Jian Xu7, Cheng-Jian Xu3, Arik Horne1, Miriam Herbert1, Anna Drews5, Charlotte Thibeault2, Moritz Pfeiffer2, Stefan Hippenstiel2, Andreas C. Hocke2, Holger Müller-Redetzky2, Katrin-Moira Heim2, Felix Machleidt2, Alexander Uhrig2, Laure Bosquillon de Jarcy2, Linda Jürgens2, Miriam Stegemann2, Christoph R. Glösenkamp2, Hans-Dieter Volk2, Christine Goffinet2, Markus Landthaler8, Emanuel Wyler8, Philipp Georg2, Maria Schneider2, Chantip Dang-Heine2, Nick Neuwinger2, Kai Kappert2, Rudolf Tauber2, Victor M. Corman2, Jan Raabe4, Kim Melanie Kaiser4, Michael To Vinh4, Gereon Rieke4, Christian Meisel2, Thomas Ulas5, Matthias Becker5, Robert Geffers, Martin Witzenrath2, Christian Drosten2, Norbert Suttorp2, Christof von Kalle2, Florian Kurth2, Florian Kurth9, Florian Kurth10, Kristian Händler5, Joachim L. Schultze1, Joachim L. Schultze5, Anna C. Aschenbrenner1, Anna C. Aschenbrenner7, Yang Li7, Yang Li3, Jacob Nattermann4, Birgit Sawitzki2, Antoine-Emmanuel Saliba, Leif E. Sander2, Angel Angelov, Robert Bals, Alexander Bartholomäus, Anke Becker, Daniela Bezdan, Ezio Bonifacio, Peer Bork, Thomas Clavel, Maria Colomé-Tatché, Andreas Diefenbach, Alexander T. Dilthey, Nicole Fischer, Konrad U. Förstner, Julia-Stefanie Frick, Julien Gagneur, Alexander Goesmann, Torsten Hain, Michael Hummel, Stefan Janssen, Jörn Kalinowski, René Kallies, Birte Kehr, Andreas Keller, Sarah Kim-Hellmuth, Christoph Klein, Oliver Kohlbacher, Jan O. Korbel, Ingo Kurth, Kerstin U. Ludwig, Oliwia Makarewicz, Manja Marz, Alice C. McHardy, Christian Mertes, Markus M. Nöthen, Peter Nürnberg, Uwe Ohler, Stephan Ossowski, Jörg Overmann, Silke Peter, Klaus Pfeffer, Anna R. Poetsch, Alfred Pühler, Nikolaus Rajewsky, Markus Ralser, Olaf Rieß, Stephan Ripke, Ulisses Nunes da Rocha, Philip Rosenstiel, Philipp H. Schiffer, Eva-Christina Schulte, Alexander Sczyrba, Oliver Stegle, Jens Stoye, Fabian J. Theis, Janne Vehreschild, Jörg Vogel, Max von Kleist, Andreas Walker, Jörn Walter, Dagmar Wieczorek, John Ziebuhr 
17 Sep 2020-Cell
TL;DR: This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

1,042 citations

Journal ArticleDOI
TL;DR: The current state of the noninvasive assessment of liver disease in NAFLD is summarized, and an expert synthesis of how these nonin invasive tools could be utilized in clinical practice is provided.

780 citations

Journal ArticleDOI
TL;DR: The status of research into important genetic and epigenetic modifiers of NAFLD progression are discussed and the potential to translate the accumulating wealth of genetic data into the design of novel therapeutics and the clinical implementation of diagnostic/prognostic biomarkers will be explored.

582 citations