TY - JOUR
A1 - Kleinert, Evelyn
A1 - Hillermann, Nele
A1 - Jablonka, Alexandra
A1 - Happle, Christine
A1 - Müller, Frank
A1 - Simmenroth, Anne
T1 - Prescription of antibiotics in the medical care of newly arrived refugees and migrants
JF - Pharmacoepidemiology and Drug Safety
N2 - Purpose
Unnecessary and inappropriate use of antibiotics is a widespread problem in primary care. However, current data on the care of refugees and migrants in initial reception centers is pending. This article provides data on prescription frequencies of various antibiotics and associated diagnoses.
Methods
In this retrospective observational study, patient data of 3255 patients with 6376 medical contacts in two initial reception centers in Germany were analyzed. Patient data, collected by chart review, included sociodemographic characteristics, diagnoses, and prescriptions. Antibiotic prescription behavior and corresponding physician‐coded diagnoses were analyzed.
Results
Nineteen percent of all patients in our study received systemic antibiotics during the observation period, with children below the age of 10 years receiving antibiotics most frequently (24%). The most commonly prescribed antibiotics were penicillins (65%), macrolides (12%), and cephalosporins (7%). The most frequent diagnoses associated with antibiotic prescription were acute tonsillitis (26%), bronchitis (21%), infections of the upper respiratory tract (14%), and urinary tract infections (10%). In case of acute bronchitis 74% of the antibiotic prescriptions were probably not indicated. In addition, we found a significant number of inappropriate prescriptions such as amoxicillin for tonsillitis (67%), and ciprofloxacin and cotrimoxazol for urinary tract infections (49%).
Conclusion
Regarding inappropriate prescription of antibiotics in refugee healthcare, this study shows a rate ranging from 8% for upper respiratory tract infections to 75% for acute bronchitis. Unnecessary use of antibiotics is a global problem contributing to gratuitous costs, side effects, and antimicrobial resistance. This research contributes to the development of stringent antibiotic stewardship regiments in the particularly vulnerable population of migrants and refugees.
KW - antibiotic prescription
KW - antimicrobial resistance
KW - inappropriate prescription
KW - pharmacoepidemiology
KW - primary healthcare
KW - refugee healthcare
KW - viral infection
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244771
VL - 30
IS - 8
SP - 1074
EP - 1083
ER -
TY - JOUR
A1 - Marquardt, André
A1 - Landwehr, Laura-Sophie
A1 - Ronchi, Cristina L.
A1 - di Dalmazi, Guido
A1 - Riester, Anna
A1 - Kollmannsberger, Philip
A1 - Altieri, Barbara
A1 - Fassnacht, Martin
A1 - Sbiera, Silviu
T1 - Identifying New Potential Biomarkers in Adrenocortical Tumors Based on mRNA Expression Data Using Machine Learning
JF - Cancers
N2 - Simple Summary
Using a visual-based clustering method on the TCGA RNA sequencing data of a large adrenocortical carcinoma (ACC) cohort, we were able to classify these tumors in two distinct clusters largely overlapping with previously identified ones. As previously shown, the identified clusters also correlated with patient survival. Applying the visual clustering method to a second dataset also including benign adrenocortical samples additionally revealed that one of the ACC clusters is more closely located to the benign samples, providing a possible explanation for the better survival of this ACC cluster. Furthermore, the subsequent use of machine learning identified new possible biomarker genes with prognostic potential for this rare disease, that are significantly differentially expressed in the different survival clusters and should be further evaluated.
Abstract
Adrenocortical carcinoma (ACC) is a rare disease, associated with poor survival. Several “multiple-omics” studies characterizing ACC on a molecular level identified two different clusters correlating with patient survival (C1A and C1B). We here used the publicly available transcriptome data from the TCGA-ACC dataset (n = 79), applying machine learning (ML) methods to classify the ACC based on expression pattern in an unbiased manner. UMAP (uniform manifold approximation and projection)-based clustering resulted in two distinct groups, ACC-UMAP1 and ACC-UMAP2, that largely overlap with clusters C1B and C1A, respectively. However, subsequent use of random-forest-based learning revealed a set of new possible marker genes showing significant differential expression in the described clusters (e.g., SOAT1, EIF2A1). For validation purposes, we used a secondary dataset based on a previous study from our group, consisting of 4 normal adrenal glands and 52 benign and 7 malignant tumor samples. The results largely confirmed those obtained for the TCGA-ACC cohort. In addition, the ENSAT dataset showed a correlation between benign adrenocortical tumors and the good prognosis ACC cluster ACC-UMAP1/C1B. In conclusion, the use of ML approaches re-identified and redefined known prognostic ACC subgroups. On the other hand, the subsequent use of random-forest-based learning identified new possible prognostic marker genes for ACC.
KW - adrenocortical carcinoma
KW - in silico analysis
KW - machine learning
KW - bioinformatic clustering
KW - biomarker prediction
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246245
SN - 2072-6694
VL - 13
IS - 18
ER -
TY - JOUR
A1 - Beierle, Felix
A1 - Schobel, Johannes
A1 - Vogel, Carsten
A1 - Allgaier, Johannes
A1 - Mulansky, Lena
A1 - Haug, Fabian
A1 - Haug, Julian
A1 - Schlee, Winfried
A1 - Holfelder, Marc
A1 - Stach, Michael
A1 - Schickler, Marc
A1 - Baumeister, Harald
A1 - Cohrdes, Caroline
A1 - Deckert, Jürgen
A1 - Deserno, Lorenz
A1 - Edler, Johanna-Sophie
A1 - Eichner, Felizitas A.
A1 - Greger, Helmut
A1 - Hein, Grit
A1 - Heuschmann, Peter
A1 - John, Dennis
A1 - Kestler, Hans A.
A1 - Krefting, Dagmar
A1 - Langguth, Berthold
A1 - Meybohm, Patrick
A1 - Probst, Thomas
A1 - Reichert, Manfred
A1 - Romanos, Marcel
A1 - Störk, Stefan
A1 - Terhorst, Yannik
A1 - Weiß, Martin
A1 - Pryss, Rüdiger
T1 - Corona Health — A Study- and Sensor-Based Mobile App Platform Exploring Aspects of the COVID-19 Pandemic
JF - International Journal of Environmental Research and Public Health
N2 - Physical and mental well-being during the COVID-19 pandemic is typically assessed via surveys, which might make it difficult to conduct longitudinal studies and might lead to data suffering from recall bias. Ecological momentary assessment (EMA) driven smartphone apps can help alleviate such issues, allowing for in situ recordings. Implementing such an app is not trivial, necessitates strict regulatory and legal requirements, and requires short development cycles to appropriately react to abrupt changes in the pandemic. Based on an existing app framework, we developed Corona Health, an app that serves as a platform for deploying questionnaire-based studies in combination with recordings of mobile sensors. In this paper, we present the technical details of Corona Health and provide first insights into the collected data. Through collaborative efforts from experts from public health, medicine, psychology, and computer science, we released Corona Health publicly on Google Play and the Apple App Store (in July 2020) in eight languages and attracted 7290 installations so far. Currently, five studies related to physical and mental well-being are deployed and 17,241 questionnaires have been filled out. Corona Health proves to be a viable tool for conducting research related to the COVID-19 pandemic and can serve as a blueprint for future EMA-based studies. The data we collected will substantially improve our knowledge on mental and physical health states, traits and trajectories as well as its risk and protective factors over the course of the COVID-19 pandemic and its diverse prevention measures.
KW - mobile health
KW - ecological momentary assessment
KW - digital phenotyping
KW - longitudinal studies
KW - mobile crowdsensing
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242658
SN - 1660-4601
VL - 18
IS - 14
ER -
TY - JOUR
A1 - Popp, Sandy
A1 - Schmitt-Böhrer, Angelika
A1 - Langer, Simon
A1 - Hofmann, Ulrich
A1 - Hommers, Leif
A1 - Schuh, Kai
A1 - Frantz, Stefan
A1 - Lesch, Klaus-Peter
A1 - Frey, Anna
T1 - 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
JF - Journal of Clinical Medicine
N2 - Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.
KW - chronic heart failure
KW - myocardial infarction
KW - serotonin transporter deficient mice
KW - anxiety
KW - depression
KW - behavior
KW - inflammation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242739
SN - 2077-0383
VL - 10
IS - 14
ER -
TY - JOUR
A1 - Sbiera, Iuliu
A1 - Kircher, Stefan
A1 - Altieri, Barbara
A1 - Fassnacht, Martin
A1 - Kroiss, Matthias
A1 - Sbiera, Silviu
T1 - Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?
JF - Cancers
N2 - A clinically relevant proportion of adrenocortical carcinoma (ACC) cases shows a tendency to metastatic spread. The objective was to determine whether the epithelial to mesenchymal transition (EMT), a mechanism associated with metastasizing in several epithelial cancers, might play a crucial role in ACC. 138 ACC, 29 adrenocortical adenomas (ACA), three normal adrenal glands (NAG), and control tissue samples were assessed for the expression of epithelial (E-cadherin and EpCAM) and mesenchymal (N-cadherin, SLUG and SNAIL) markers by immunohistochemistry. Using real-time RT-PCR we quantified the alternative isoform splicing of FGFR 2 and 3, another known indicator of EMT. We also assessed the impact of these markers on clinical outcome. Results show that both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers but strongly expressed mesenchymal markers N-cadherin and SLUG. FGFR isoform splicing confirmed higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues. In ACC, higher SLUG expression was associated with clinical markers indicating aggressiveness, while N-cadherin expression inversely associated with these markers. In conclusion, we could not find any indication of EMT as all adrenocortical tissues lacked expression of epithelial markers and exhibited closer similarity to mesenchymal tissues. However, while N-cadherin might play a positive role in tissue structure upkeep, SLUG seems to be associated with a more aggressive phenotype.
KW - adrenocortical tissues
KW - EMT
KW - epithelial markers
KW - mesenchymal markers
KW - recurrence-free survival
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236486
SN - 2072-6694
VL - 13
IS - 7
ER -
TY - JOUR
A1 - Detomas, Mario
A1 - Altieri, Barbara
A1 - Schlötelburg, Wiebke
A1 - Appenzeller, Silke
A1 - Schlaffer, Sven
A1 - Coras, Roland
A1 - Schirbel, Andreas
A1 - Wild, Vanessa
A1 - Kroiss, Matthias
A1 - Sbiera, Silviu
A1 - Fassnacht, Martin
A1 - Deutschbein, Timo
T1 - Case Report: Consecutive Adrenal Cushing’s Syndrome and Cushing’s Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations
JF - Frontiers in Endocrinology
N2 - The occurrence of different subtypes of endogenous Cushing’s syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing’s disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.
KW - Cushing’s syndrome
KW - Cushing’s disease
KW - hypercortisolism
KW - glucocorticoid excess
KW - USP8
KW - CTNNB1
KW - NR3C1
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244596
SN - 1664-2392
VL - 12
ER -
TY - JOUR
A1 - Adam, Pia
A1 - Kircher, Stefan
A1 - Sbiera, Iuliu
A1 - Koehler, Viktoria Florentine
A1 - Berg, Elke
A1 - Knösel, Thomas
A1 - Sandner, Benjamin
A1 - Fenske, Wiebke Kristin
A1 - Bläker, Hendrik
A1 - Smaxwil, Constantin
A1 - Zielke, Andreas
A1 - Sipos, Bence
A1 - Allelein, Stephanie
A1 - Schott, Matthias
A1 - Dierks, Christine
A1 - Spitzweg, Christine
A1 - Fassnacht, Martin
A1 - Kroiss, Matthias
T1 - FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale
JF - Frontiers in Endocrinology
N2 - Background
Treatment options for poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is approved for advanced radioiodine refractory thyroid carcinoma, but response to single agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor pembrolizumab (PEM) are promising.
Materials and Methods
Primary ATC (n=93) and PDTC (n=47) tissue samples diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1 expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4 mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization. Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls. Disease specific survival (DSS) was the primary outcome variable.
Results
PD-L1 TPS≥50% was observed in 42% of ATC and 26% of PDTC specimens. Mean PD-L1 expression was significantly higher in ATC (TPS 30%) than in PDTC (5%; p<0.01) and NT (0%, p<0.001). 53% of PDTC samples had PD-L1 expression ≤5%. FGFR mRNA expression was generally low in all samples but combined FGFR1-4 expression was significantly higher in PDTC and ATC compared to NT (each p<0.001). No impact of PD-L1 and FGFR 1-4 expression was observed on DSS.
Conclusion
High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is low thyroid tumor cells. The clinically observed synergism of PEM with LEN may be caused by immune modulation.
KW - tyrosine kinase inhibitor (TKI)
KW - immune checkpoint inhibitor (ICI)
KW - immunohistochemistry
KW - immunotherapy
KW - PD-L1
KW - FGFR
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244653
SN - 1664-2392
VL - 12
ER -
TY - JOUR
A1 - Reinecke, Holger
A1 - Jürgensmeyer, Sabine
A1 - Engelbertz, Christiane
A1 - Gerss, Joachim
A1 - Kirchhof, Paulus
A1 - Breithardt, Günter
A1 - Bauersachs, Rupert
A1 - Wanner, Christoph
T1 - Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA-AFNET 8 study
JF - BMJ open
N2 - Introduction Patients with end-stage kidney disease requiring maintenance haemodialysis treatment experience a dramatic cardiovascular morbidity and mortality. Due to the high atherosclerotic and arteriosclerotic burden and profound alterations in haemostasis, they frequently suffer and die from both thromboembolic and bleeding events. This is a particular concern in patients on haemodialysis with atrial fibrillation (AF). Controlled trials on the optimal anticoagulation in patients with AF on haemodialysis are not available. The randomised controlled phase IIIb AXADIA-AFNET 8 trial will evaluate the safety and efficacy of the factor Xa inhibitor apixaban in patients with AF requiring haemodialysis. Methods and analysis A total of 222 patients will be randomised in an open-labelled, 1:1 design to receive either apixaban 2.5mg twice daily or dose-adjusted vitamin K antagonist therapy (target international normalised ratio 2.0-3.0). All patients will be treated and followed up for a minimum of 6 months up to a maximum of 24 months. The primary outcome is major or clinically relevant, non-major bleedings or death of any cause. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, thus exploring the efficacy of apixaban. The first patient was randomised in June 2017. Ethics and dissemination The study protocol was approved by the Ethical Committee of the Landesaertzekammer, Westfalen-Lippe and the Medical Faculty of the University of Muenster, Muenster, Germany (reference number: 2016-598f-A). Written informed consent will be obtained from all patients prior to study participation, including their consent for long-term follow-up. AXADIA-AFNET 8 is an investigator-initiated trial. Sponsor is AFNET, Muenster, Germany. Study findings will be disseminated to Bristol-Myers Squibb, Munich, Germany, and Pfizer, Berlin, Germany, to the participating centres, at research conferences and in peer-reviewed journals. Trial registration numbers NCT02933697, Pre-results.
KW - arial fibrillation
KW - hemodialysis
KW - cardiovascular morbidity
KW - cardiovascular mortality
KW - anticoagulation
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225156
VL - 8
IS - 9
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
A1 - Buck, Andreas K.
A1 - Hartrampf, Philipp E.
A1 - Serfling, Sebastian E.
A1 - Scheurlen, Michael
A1 - Wester, Hans-Jürgen
A1 - Meining, Alexander
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF - Diagnostics
N2 - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW - CXCR4
KW - NET
KW - NEC
KW - 68Ga-Pentixafor
KW - 18F-FDG
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN - 2075-4418
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Andelovic, Kristina
A1 - Winter, Patrick
A1 - Jakob, Peter Michael
A1 - Bauer, Wolfgang Rudolf
A1 - Herold, Volker
A1 - Zernecke, Alma
T1 - Evaluation of plaque characteristics and inflammation using magnetic resonance imaging
JF - Biomedicines
N2 - Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth. There is also evidence that low and oscillatory shear stress contribute to arterial remodeling, entailing a loss in arterial elasticity and, therefore, an increased pulse-wave velocity. Although altered shear stress profiles, elasticity and inflammation are closely intertwined and critical for plaque growth, preclinical and clinical investigations for atherosclerosis mostly focus on the investigation of one of these parameters only due to the experimental limitations. However, cardiovascular magnetic resonance imaging (MRI) has been demonstrated to be a potent tool which can be used to provide insights into a large range of biological parameters in one experimental session. It enables the evaluation of the dynamic process of atherosclerotic lesion formation without the need for harmful radiation. Flow-sensitive MRI provides the assessment of hemodynamic parameters such as wall shear stress and pulse wave velocity which may replace invasive and radiation-based techniques for imaging of the vascular
function and the characterization of early plaque development. In combination with inflammation imaging, the analyses and correlations of these parameters could not only significantly advance basic preclinical investigations of atherosclerotic lesion formation and progression, but also the diagnostic clinical evaluation for early identification of high-risk plaques, which are prone to rupture. In this review, we summarize the key applications of magnetic resonance imaging for the evaluation of plaque characteristics through flow sensitive and morphological measurements. The simultaneous measurements of functional and structural parameters will further preclinical research on atherosclerosis and has the potential to fundamentally improve the detection of inflammation and vulnerable plaques in patients.
KW - atherosclerosis
KW - mouse models
KW - wall shear stress
KW - pulse wave velocity
KW - arterial elasticity
KW - inflammation
KW - magnetic resonance imaging
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228839
SN - 2227-9059
VL - 9
IS - 2
ER -
TY - JOUR
A1 - Rickert, V.
A1 - Wagenhäuser, L.
A1 - Nordbeck, P.
A1 - Wanner, C.
A1 - Sommer, C.
A1 - Rost, S.
A1 - Üçeyler, N.
T1 - Stratification of Fabry mutations in clinical practice: a closer look at α‐galactosidase A‐3D structure
JF - Journal of Internal Medicine
N2 - Background
Fabry disease (FD) is an X‐linked lysosomal storage and multi‐system disorder due to mutations in the α‐galactosidase A (α‐GalA) gene. We investigated the impact of individual amino acid exchanges in the α‐GalA 3D‐structure on the clinical phenotype of FD patients.
Patients and methods
We enrolled 80 adult FD patients with α‐GalA missense mutations and stratified them into three groups based on the amino acid exchange location in the α‐GalA 3D‐structure: patients with active site mutations, buried mutations and other mutations. Patient subgroups were deep phenotyped for clinical and laboratory parameters and FD‐specific treatment.
Results
Patients with active site or buried mutations showed a severe phenotype with multi‐organ involvement and early disease manifestation. Patients with other mutations had a milder phenotype with less organ impairment and later disease onset. α‐GalA activity was lower in patients with active site or buried mutations than in those with other mutations (P < 0.01 in men; P < 0.05 in women) whilst lyso‐Gb3 levels were higher (P < 0.01 in men; <0.05 in women).
Conclusions
The type of amino acid exchange location in the α‐GalA 3D‐structure determines disease severity and temporal course of symptom onset. Patient stratification using this parameter may become a useful tool in the management of FD patients.
KW - Fabry disease
KW - Fabry genotype
KW - Fabry phenotype
KW - lyso‐Gb3
KW - α‐GalA 3D‐structure
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218125
VL - 288
IS - 5
SP - 593
EP - 604
ER -
TY - JOUR
A1 - Kraft, Peter
A1 - Drechsler, Christiane
A1 - Gunreben, Ignaz
A1 - Heuschmann, Peter Ulrich
A1 - Kleinschnitz, Christoph
T1 - Regulation of Blood Coagulation Factors XI and XII in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study
JF - Cerebrovascular Diseases
N2 - Background: Animal models have implicated an integral role for coagulation factors XI (FXI) and XII (FXII) in thrombus formation and propagation of ischemic stroke (IS). However, it is unknown if these molecules contribute to IS pathophysiology in humans, and might be of use as biomarkers for IS risk and severity. This study aimed to identify predictors of altered FXI and FXII levels and to determine whether there are differences in the levels of these coagulation factors between acute cerebrovascular events and chronic cerebrovascular disease (CCD). Methods: In this case-control study, 116 patients with acute ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD, and 104 healthy volunteers (HVs) were enrolled between 2010 and 2013 at our University hospital. Blood sampling was undertaken once in the CCD and HV groups and on days 0, 1, and 3 after stroke onset in patients with AIS or TIA. Correlations between serum FXI and FXII levels and demographic and clinical parameters were tested by linear regression and analysis of variance. Results: The mean age of AIS/TIA patients was 70 ± 12. Baseline clinical severity measured with NIHSS and Barthel Index was 4.8 ± 6.0 and 74 ± 30, respectively. More than half of the patients had an AIS (58%). FXI levels were significantly correlated with different leukocyte subsets (p < 0.05). In contrast, FXII serum levels showed no significant correlation (p > 0.1). Neither FXI nor FXII levels correlated with CRP (p > 0.2). FXII levels were significantly higher in patients with CCD compared with those with AIS/TIA (mean ± SD 106 ± 26% vs. 97 ± 24%; univariate analysis: p < 0.05); these differences did not reach significance in multivariate analysis adjusted for sex and age. FXI levels did not differ significantly between study groups. Sex and age were significantly associated with FXI and/or FXII levels in patients with AIS/TIA (p < 0.05). In contrast, no statistical significant influence was found for treatment modality (thrombolysis or not), pre-treatment with platelet inhibitors, and severity of stroke. Conclusions: In this study, there was no differential regulation of FXI and FXII levels between disease subtypes but biomarker levels were associated with patient and clinical characteristics. FXI and FXII levels might be no valid biomarker for predicting stroke risk.
KW - biomarker
KW - factor XI
KW - factor XII
KW - ischemic stroke
KW - chronic cerebrovascular disease
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199076
SN - 1015-9770
SN - 1421-9786
N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL - 38
IS - 5
ER -
TY - JOUR
A1 - Hock, Michael
A1 - Terekhov, Maxim
A1 - Stefanescu, Maria Roxana
A1 - Lohr, David
A1 - Herz, Stefan
A1 - Reiter, Theresa
A1 - Ankenbrand, Markus
A1 - Kosmala, Aleksander
A1 - Gassenmaier, Tobias
A1 - Juchem, Christoph
A1 - Schreiber, Laura Maria
T1 - B\(_{0}\) shimming of the human heart at 7T
JF - Magnetic Resonance in Medicine
N2 - Purpose
Inhomogeneities of the static magnetic B\(_{0}\) field are a major limiting factor in cardiac MRI at ultrahigh field (≥ 7T), as they result in signal loss and image distortions. Different magnetic susceptibilities of the myocardium and surrounding tissue in combination with cardiac motion lead to strong spatio‐temporal B\(_{0}\)‐field inhomogeneities, and their homogenization (B0 shimming) is a prerequisite. Limitations of state‐of‐the‐art shimming are described, regional B\(_{0}\) variations are measured, and a methodology for spherical harmonics shimming of the B\(_{0}\) field within the human myocardium is proposed.
Methods
The spatial B\(_{0}\)‐field distribution in the heart was analyzed as well as temporal B\(_{0}\)‐field variations in the myocardium over the cardiac cycle. Different shim region‐of‐interest selections were compared, and hardware limitations of spherical harmonics B\(_{0}\) shimming were evaluated by calibration‐based B0‐field modeling. The role of third‐order spherical harmonics terms was analyzed as well as potential benefits from cardiac phase–specific shimming.
Results
The strongest B\(_{0}\)‐field inhomogeneities were observed in localized spots within the left‐ventricular and right‐ventricular myocardium and varied between systolic and diastolic cardiac phases. An anatomy‐driven shim region‐of‐interest selection allowed for improved B\(_{0}\)‐field homogeneity compared with a standard shim region‐of‐interest cuboid. Third‐order spherical harmonics terms were demonstrated to be beneficial for shimming of these myocardial B\(_{0}\)‐field inhomogeneities. Initial results from the in vivo implementation of a potential shim strategy were obtained. Simulated cardiac phase–specific shimming was performed, and a shim term‐by‐term analysis revealed periodic variations of required currents.
Conclusion
Challenges in state‐of‐the‐art B\(_{0}\) shimming of the human heart at 7 T were described. Cardiac phase–specific shimming strategies were found to be superior to vendor‐supplied shimming.
KW - 7 T
KW - B
KW - cardiac MRI
KW - shimming
KW - ultrahigh field
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218096
VL - 85
IS - 1
SP - 182
EP - 196
ER -
TY - JOUR
A1 - Schneider, Andreas
A1 - Gutjahr-Lengsfeld, Lena
A1 - Ritz, Eberhard
A1 - Scharnagl, Hubert
A1 - Gelbrich, Götz
A1 - Pilz, Stefan
A1 - Macdougall, Iain C.
A1 - Wanner, Christoph
A1 - Drechsler, Christiane
T1 - Longitudinal Assessments of Erythropoietin-Stimulating Agent Responsiveness and the Association with Specific Clinical Outcomes in Dialysis Patients
JF - Nephron Clinical Practice
N2 - Background: Dose requirements of erythropoietin-stimulating agents (ESAs) can vary considerably over time and may be associated with cardiovascular outcomes. We aimed to longitudinally assess ESA responsiveness over time and to investigate its association with specific clinical end points in a time-dependent approach. Methods: The German Diabetes and Dialysis study (4D study) included 1,255 diabetic dialysis patients, of whom 1,161 were receiving ESA treatment. In those patients, the erythropoietin resistance index (ERI) was assessed every 6 months during a median follow-up of 4 years. The association between the ERI and cardiovascular end points was analyzed by time-dependent Cox regression analyses with repeated ERI measures. Results: Patients had a mean age of 66 ± 8.2 years; 53% were male. During follow-up, a total of 495 patients died, of whom 136 died of sudden death and 102 of infectious death. The adjusted and time-dependent risk for sudden death was increased by 19% per 5-unit increase in the ERI (hazard ratio, HR = 1.19, 95% confidence interval, CI = 1.07-1.33). Similarly, mortality increased by 25% (HR = 1.25, 95% CI = 1.18-1.32) and infectious death increased by 27% (HR = 1.27, 95% CI = 1.13-1.42). Further analysis revealed that lower 25-hydroxyvitamin D levels were associated with lower ESA responsiveness (p = 0.046). Conclusions: In diabetic dialysis patients, we observed that time-varying erythropoietin resistance is associated with sudden death, infectious complications and all-cause mortality. Low 25-hydroxyvitamin D levels may contribute to a lower ESA responsiveness.
KW - dialysis
KW - erythropoietin
KW - diabetes
KW - epidemiology
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196511
SN - 1660-2110
N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL - 128
IS - 1-2
ER -
TY - JOUR
A1 - de Zeeuw, Dick
A1 - Akizawa, Tadao
A1 - Agarwal, Rajiv
A1 - Audhya, Paul
A1 - Bakris, George L.
A1 - Chin, Melanie
A1 - Krauth, Melissa
A1 - Lambers Heerspink, Hiddo J.
A1 - Meyer, Colin J.
A1 - McMurray, John J.
A1 - Parving, Hans-Henrik
A1 - Pergola, Pablo E.
A1 - Remuzzi, Giuseppe
A1 - Toto, Robert D.
A1 - Vaziri, Nosratola D.
A1 - Wanner, Christoph
A1 - Warnock, David G.
A1 - Wittes, Janet
A1 - Chertow, Glenn M.
T1 - Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON)
JF - American Journal of Nephrology
N2 - Background: Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. Methods: Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. Results: The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. Conclusion: BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.
KW - clinical trial
KW - diabetes mellitus
KW - glomerular filtration rate
KW - trial design
KW - bardoxolone methyl
KW - Nrf2
KW - end-stage renal disease
KW - cardiovascular death
KW - chronic kidney disease
Y1 - 2013
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196832
SN - 0250-8095
SN - 1421-9670
N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL - 37
IS - 3
ER -
TY - JOUR
A1 - Eiringhaus, Jörg
A1 - Wünsche, Christoph M.
A1 - Tirilomis, Petros
A1 - Herting, Jonas
A1 - Bork, Nadja
A1 - Nikolaev, Viacheslav O.
A1 - Hasenfuss, Gerd
A1 - Sossalla, Samuel
A1 - Fischer, Thomas H.
T1 - Sacubitrilat reduces pro‐arrhythmogenic sarcoplasmic reticulum Ca\(^{2+}\) leak in human ventricular cardiomyocytes of patients with end‐stage heart failure
JF - ESC Heart Failure
N2 - Aims
Inhibition of neprilysin and angiotensin II receptor by sacubitril/valsartan (Val) (LCZ696) reduces mortality in heart failure (HF) patients compared with sole inhibition of renin–angiotensin system. Beneficial effects of increased natriuretic peptide levels upon neprilysin inhibition have been proposed, whereas direct effects of sacubitrilat (Sac) (LBQ657) on myocardial Ca\(^{2+}\) cycling remain elusive.
Methods and results
Confocal microscopy (Fluo‐4 AM) was used to investigate pro‐arrhythmogenic sarcoplasmic reticulum (SR) Ca\(^{2+}\) leak in freshly isolated murine and human ventricular cardiomyocytes (CMs) upon Sac (40 μmol/L)/Val (13 μmol/L) treatment. The concentrations of Sac and Val equalled plasma concentrations of LCZ696 treatment used in PARADIGM‐HF trial. Epifluorescence microscopy measurements (Fura‐2 AM) were performed to investigate effects on systolic Ca\(^{2+}\) release, SR Ca\(^{2+}\) load, and Ca\(^{2+}\)‐transient kinetics in freshly isolated murine ventricular CMs. The impact of Sac on myocardial contractility was evaluated using in toto‐isolated, isometrically twitching ventricular trabeculae from human hearts with end‐stage HF. Under basal conditions, the combination of Sac/Val did not influence diastolic Ca\(^{2+}\)‐spark frequency (CaSpF) nor pro‐arrhythmogenic SR Ca\(^{2}\) leak in isolated murine ventricular CMs (n CMs/hearts = 80/7 vs. 100/7, P = 0.91/0.99). In contrast, Sac/Val treatment reduced CaSpF by 35 ± 9% and SR Ca\(^{2+}\) leak by 45 ± 9% in CMs put under catecholaminergic stress (isoproterenol 30 nmol/L, n = 81/7 vs. 62/7, P < 0.001 each). This could be attributed to Sac, as sole Sac treatment also reduced both parameters by similar degrees (reduction of CaSpF by 57 ± 7% and SR Ca2+ leak by 76 ± 5%; n = 101/4 vs. 108/4, P < 0.01 each), whereas sole Val treatment did not. Systolic Ca2+ release, SR Ca\(^{2+}\) load, and Ca\(^{2+}\)‐transient kinetics including SERCA activity (k\(_{SERCA}\)) were not compromised by Sac in isolated murine CMs (n = 41/6 vs. 39/6). Importantly, the combination of Sac/Val and Sac alone also reduced diastolic CaSpF and SR Ca\(^{2+}\) leak (reduction by 74 ± 7%) in human left ventricular CMs from patients with end‐stage HF (n = 71/8 vs. 78/8, P < 0.05 each). Myocardial contractility of human ventricular trabeculae was not acutely affected by Sac treatment as the developed force remained unchanged over a time course of 30 min (n trabeculae/hearts = 3/3 vs. 4/3).
Conclusion
This study demonstrates that neprilysin inhibitor Sac directly improves Ca\(^{2+}\) homeostasis in human end‐stage HF by reducing pro‐arrhythmogenic SR Ca\(^{2+}\) leak without acutely affecting systolic Ca\(^{2+}\) release and inotropy. These effects might contribute to the mortality benefits observed in the PARADIGM‐HF trial.
KW - heart failure
KW - entresto
KW - Neprilysin inhibition
KW - Ca cycling
KW - SR Ca leak
KW - arrhythmia
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218479
VL - 7
IS - 5
SP - 2992
EP - 3002
ER -
TY - JOUR
A1 - Rogowski-Lehmann, Natalie
A1 - Geroula, Aikaterini
A1 - Prejbisz, Aleksander
A1 - Timmers, Henri J. L. M.
A1 - Megerle, Felix
A1 - Robledo, Mercedes
A1 - Fassnacht, Martin
A1 - Fliedner, Stephanie M. J.
A1 - Reincke, Martin
A1 - Stell, Anthony
A1 - Januszewicz, Andrzej
A1 - Lenders, Jacques W. M.
A1 - Eisenhofer, Graeme
A1 - Beuschlein, Felix
T1 - Missed clinical clues in patients with pheochromocytoma/paraganglioma discovered by imaging
JF - Endocrine Connections
N2 - Background: Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure. Objective: To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL). Design: Prospective study protocol, which has enrolled patients from six European centers with confirmed PPGLs. Data were analyzed from 235 patients (37 iPPGLs, 36 sPPGLs, 27% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. iPPGL patients were diagnosed at a significantly higher age than fPPGLs (P<0.001), found to have larger tumors (P=0.003) and higher metanephrine and normetanephrine levels at diagnosis (P=0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs 4.3 symptoms, P< 0.001). In 16.2% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than that in fPPGL (60.9%) and sPPGL (21.5%). Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients, the PPGL diagnosis had been delayed. Precis: Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes.
KW - pheochromocytoma
KW - paraganglioma
KW - imaging
KW - signs and symptoms
KW - prospective
KW - Biochemical-Diagnosis
KW - Plasma
KW - MASS
KW - Normetanephrine
KW - Metanephrine
KW - Paraganglioma
KW - Society
KW - Utility
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226481
VL - 7
IS - 11
ER -
TY - JOUR
A1 - Sailer, Clara Odilia
A1 - Wiedemann, Sophia Julia
A1 - Strauss, Konrad
A1 - Schnyder, Ingeborg
A1 - Fenske, Wiebke Kristin
A1 - Christ-Crain, Mirjam
T1 - Markers of systemic inflammation in response to osmotic stimulus in healthy volunteers
JF - Endocrine Connections
N2 - Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interle ukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium >= 150 mmol/L) by hypertonic saline infusion. Copeptin - a marker indicating vasopressin activity - serum sodium and osmolality, plasma IL-8 and TNF-alpha were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-alpha levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.1 2, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation.
KW - TNF-alpha
KW - interleukin-8
KW - interleukin-6
KW - copeptin
KW - hyperosmolality
KW - Hyperosmotic Stress
KW - Interleukin-6
KW - Expression
KW - Protein
KW - Neurons
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227204
VL - 8
IS - 9
ER -
TY - JOUR
A1 - Refardt, Julie
A1 - Sailer, Clara Odilia
A1 - Winzeler, Bettina
A1 - Betz, Matthias Johannes
A1 - Chifu, Irina
A1 - Schnyder, Ingeborg
A1 - Fassnacht, Martin
A1 - Fenske, Wiebke
A1 - Christ-Crain, Mirjam
T1 - FGF-21 levels in polyuria-polydipsia syndrome
JF - Endocrine Connections
N2 - The pathomechanism of primary polydipsia is poorly understood. Recent animal data reported a connection between fibroblast growth factor 21 (FGF-21) and elevated fluid intake independently of hormonal control by the hormone arginine-vasopressin (AVP) and osmotic stimulation. We therefore compared circulating FGF-21 levels in patients with primary polydipsia to patients with AVP deficiency (central diabetes insipidus) and healthy volunteers. In this prospective cohort study, we analyzed FGF-21 levels of 20 patients with primary polydipsia, 20 patients with central diabetes insipidus and 20 healthy volunteers before and after stimulation with hypertonic saline infusion targeting a plasma sodium level >= 150 mmol/L. The primary outcome was the difference in FGF-21 levels between the three groups. Baseline characteristics were similar between the groups except for patients with central diabetes insipidus being heavier. There was no difference in baseline FGF-21 levels between patients with primary polydipsia and healthy volunteers (122 pg/mL (52,277) vs 193 pg/mL (48,301), but higher levels in patients with central diabetes insipidus were observed (306 pg/mL (114,484); P=0.037). However, this was not confirmed in a multivariate linear regression analysis after adjusting for age, sex, BMI and smoking status. Osmotic stimulation did not affect FGF-21 levels in either group (difference to baseline: primary polydipsia -23 pg/mL (-43, 22); central diabetes insipidus 17 pg/mL (-76, 88); healthy volunteers -6 pg/mL (-68, 22); P=0.45). To conclude, FGF-21 levels are not increased in patients with primary polydipsia as compared to central diabetes insipidus or healthy volunteers. FGF-21 therefore does not seem to be causal of elevated fluid intake in these patients.
KW - FGF21
KW - diabetes insipidus
KW - primary polydipsia
KW - osmotic stimulation
KW - copeptin
KW - Fibroblast Growth Factor-21
KW - Klotho-related molecules
KW - Copeptin
KW - Diagnosis
KW - PF-05231023
KW - Resistance
KW - Men
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225085
VL - 7
IS - 12
ER -
TY - JOUR
A1 - Notz, Quirin
A1 - Lotz, Christopher
A1 - Herrmann, Johannes
A1 - Vogt, Marius
A1 - Schlesinger, Tobias
A1 - Kredel, Markus
A1 - Muellges, Wolfgang
A1 - Weismann, Dirk
A1 - Westermaier, Thomas
A1 - Meybohm, Patrick
A1 - Kranke, Peter
T1 - Severe neurological complications in critically ill COVID‑19 patients
JF - Journal of Neurology
N2 - No abstract available.
KW - COVID-19
KW - neurological complications
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232429
SN - 0340-5354
ER -