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Book ; Online ; Thesis: Evaluierung der Potenz von glykosylierten Impfstoffen am Beispiel des RSV-F Proteins

Radke, Lars [Verfasser]

2019

Author's details	Lars Radke
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Medizinische Fakultät Charité - Universitätsmedizin Berlin
Publishing place	Berlin
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: Biomarkers for Liquid Biopsies of Pituitary Neuroendocrine Tumors.

Gossing, Wilhelm / Frohme, Marcus / Radke, Lars

Biomedicines

2020 Volume 8, Issue 6

Abstract: Pituitary neuroendocrine tumors (PitNET) do not only belong to the most common intracranial neoplasms but seem to be generally more common than has been thought. Minimally invasive liquid biopsies have the potential to improve their early screening ... ...

Abstract	Pituitary neuroendocrine tumors (PitNET) do not only belong to the most common intracranial neoplasms but seem to be generally more common than has been thought. Minimally invasive liquid biopsies have the potential to improve their early screening efficiency as well as monitor prognosis by facilitating the diagnostic procedures. This review aims to assess the potential of using liquid biopsies of different kinds of biomarker species that have only been obtained from solid pituitary tissues so far. Numerous molecules have been associated with the development of a PitNET, suggesting that it often develops from the cumulative effects of many smaller genetic or epigenetic changes. These minor changes eventually pile up to switch critical molecules into tumor-promoting states, which may be the key regulatory nodes representing the most potent marker substances for a diagnostic test. Drugs targeting these nodes may be superior for the therapeutic outcome and therefore the identification of such pituitary-specific cellular key nodes will help to accelerate their application in medicine. The ongoing genetic degeneration in pituitary adenomas suggests that repeated tumor profiling via liquid biopsies will be necessary for personalized and effective treatment solutions.
Language	English
Publishing date	2020-06-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines8060148
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Contrast medium free selective adrenal vein sampling in the management of primary aldosteronism.

Boschheidgen, Matthias / Kantauskaite, Marta / Stegbauer, Johannes / Wenker, Kira / Dringenberg, Till / Radke, Karl-Ludger / Ullrich, Tim / Krieg, Andreas / Steuwe, Andrea / Minko, Peter / Schott, Matthias / Rump, Lars Christian / Antoch, Gerald / Schimmöller, Lars

Clinical imaging

2023 Volume 99, Page(s) 25–30

Abstract: Background: To analyze contrast free adrenal vein sampling (AVS) for differentiating unilateral from bilateral disease in patients diagnosed with hypertension due to primary aldosteronism (PA).: Methods: Consecutive patients with PA and subsequent ... ...

Abstract	Background: To analyze contrast free adrenal vein sampling (AVS) for differentiating unilateral from bilateral disease in patients diagnosed with hypertension due to primary aldosteronism (PA). Methods: Consecutive patients with PA and subsequent contrast medium free AVS between April 2015 and March 2020 were retrospectively included. Cross-sectional imaging (CSI), AVS and clinical data were analyzed regarding diagnostic performance. In addition, patients with lateralisation receiving adrenalectomy were compared to a control group treated with mineralocorticoid antagonists. Results: In total 186 patients with AVS were included. The success rate for bilateral catheterization was 88% (median effective dose 2.8 mSv). CSI had an accuracy of 60% (CI: 0.52-0.67) in the detection of lateralization compared to AVS. Patients with bilateral adrenal hyperplasia and those with aldosterone-producing adenoma did not differ in systolic blood pressure (sBP) (p = 0.63) or number of antihypertensive drugs (NAD) (p = 0.11). After adrenalectomy, 28 patients were cured (51%; sBP ≤130 mmHg, NAD = 0), 18 were improved (33%; decrease of sBP ≥20 mmHg and NAD), and 8 were unchanged (15%). Serum renin increased significantly after treatment (p < 0.01). Conclusion: Contrast medium free AVS is a reliable procedure in the diagnostic management of patients with PA with high technical success rate. The accordance between CSI and results from AVS was only moderate indicating the central role of AVS in the diagnostic work-up of patients with PA. Patients with predominant disease diagnosed with AVS had a high cure rate and/or significant improvement after adrenalectomy.
MeSH term(s)	Humans ; Adrenal Glands/diagnostic imaging ; Hyperaldosteronism/diagnosis ; Hyperaldosteronism/drug therapy ; Retrospective Studies ; NAD ; Adrenalectomy
Chemical Substances	NAD (0U46U6E8UK)
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1028123-x
ISSN	1873-4499 ; 0899-7071
ISSN (online)	1873-4499
ISSN	0899-7071
DOI	10.1016/j.clinimag.2023.04.002
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Article ; Online: Biomarkers for Liquid Biopsies of Pituitary Neuroendocrine Tumors

Wilhelm Gossing / Marcus Frohme / Lars Radke

Biomedicines, Vol 8, Iss 148, p

2020 Volume 148

Abstract	Pituitary neuroendocrine tumors (PitNET) do not only belong to the most common intracranial neoplasms but seem to be generally more common than has been thought. Minimally invasive liquid biopsies have the potential to improve their early screening efficiency as well as monitor prognosis by facilitating the diagnostic procedures. This review aims to assess the potential of using liquid biopsies of different kinds of biomarker species that have only been obtained from solid pituitary tissues so far. Numerous molecules have been associated with the development of a PitNET, suggesting that it often develops from the cumulative effects of many smaller genetic or epigenetic changes. These minor changes eventually pile up to switch critical molecules into tumor-promoting states, which may be the key regulatory nodes representing the most potent marker substances for a diagnostic test. Drugs targeting these nodes may be superior for the therapeutic outcome and therefore the identification of such pituitary-specific cellular key nodes will help to accelerate their application in medicine. The ongoing genetic degeneration in pituitary adenomas suggests that repeated tumor profiling via liquid biopsies will be necessary for personalized and effective treatment solutions.
Keywords	pituitary ; biomarker ; liquid biopsies ; cfRNA ; ctDNA ; miRNA ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The ElonginB/C-Cullin5-SOCS-Box-Complex Is a Potential Biomarker for Growth Hormone Disorders.

Gossing, Wilhelm / Radke, Lars / Biering, Henrik / Diederich, Sven / Mai, Knut / Frohme, Marcus

Biomedicines

2021 Volume 9, Issue 2

Abstract: Insulin-like growth factor 1 (IGF-1) is the standard biochemical marker for the diagnosis and treatment control of acromegaly and growth hormone deficiency (GHD). However, its limitations necessitate the screening for new specific and sensitive ... ...

Abstract	Insulin-like growth factor 1 (IGF-1) is the standard biochemical marker for the diagnosis and treatment control of acromegaly and growth hormone deficiency (GHD). However, its limitations necessitate the screening for new specific and sensitive biomarkers. The elonginB/C-cullin5-SOCS-box-complex (ECS-complex) (an intracellular five-protein complex) is stimulated by circulating growth hormone (GH) and regulates GH receptor levels through a negative feedback loop. It mediates the cells' sensitivity for GH and therefore, represents a potent new biomarker for those diseases. In this study, individual ECS-complex proteins were measured in whole blood samples of patients with acromegaly (n = 32) or GHD (n = 12) via ELISA and compared to controls. Hierarchical clustering of the results revealed that by combining the three ECS-complex proteins suppressor of cytokine signaling 2 (SOCS2), cullin-5 and ring-box protein 2 (Rbx-2), 93% of patient samples could be separated from controls, despite many patients having a normal IGF-1 or not receiving medical treatment. SOCS2 showed the best individual diagnostic performance with an overall accuracy of 0.93, while the combination of the three proteins correctly identified all patients and controls. This resulted in perfect sensitivity and specificity for all patient groups, which demonstrates potential benefits of the ECS-complex proteins as clinical biomarkers for the diagnostics of GH-related diseases and substantiates their important role in GH metabolism.
Language	English
Publishing date	2021-02-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9020201
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Article ; Online: Incidence and predictors of left atrial appendage thrombus on transesophageal echocardiography before elective cardioversion.

Wegner, Felix K / Radke, Robert / Ellermann, Christian / Wolfes, Julian / Fischer, Alicia J / Baumgartner, Helmut / Eckardt, Lars / Diller, Gerhard-Paul / Orwat, Stefan

Scientific reports

2022 Volume 12, Issue 1, Page(s) 3671

Abstract: Guidelines recommend transesophageal echocardiography (TEE) before cardioversion in thrombogenic arrhythmias when the requirement of ≥ 3 weeks of anticoagulation is not met. Current data to support this approach, especially with direct oral ... ...

Abstract	Guidelines recommend transesophageal echocardiography (TEE) before cardioversion in thrombogenic arrhythmias when the requirement of ≥ 3 weeks of anticoagulation is not met. Current data to support this approach, especially with direct oral anticoagulants (DOAC), are scarce. We analyzed consecutive elective pre-cardioversion TEE in a high-volume electrophysiology center for the occurrence of left atrial appendage (LAA) thrombi or reduced LAA flow velocity. Possible predictors were recorded and compared in a multivariate logistic regression analysis. Consecutive pre-cardioversion TEE in 512 patients (148 female, median age 69 years) were included. In all patients, indication for TEE was either intake of anticoagulation < 3 weeks before cardioversion or uncertain adherence to the prescribed anticoagulation regimen. Of the 512 TEE, 19 (3.7%) depicted a LAA thrombus. An additional 41 patients (8.0%) showed either a reduced LAA flow velocity (≤ 20 cm/s), LAA sludge, or both. In a multivariate logistic regression analysis, QRS width on admission 12-lead ECG emerged as a possible predictor of LAA thrombus and reduced LAA flow (p = 0.008). Noteworthy, a high CHA
MeSH term(s)	Aged ; Anticoagulants/therapeutic use ; Atrial Appendage/diagnostic imaging ; Atrial Fibrillation/complications ; Atrial Fibrillation/diagnostic imaging ; Atrial Fibrillation/therapy ; Echocardiography, Transesophageal ; Electric Countershock/adverse effects ; Female ; Heart Diseases ; Humans ; Incidence ; Male ; Thrombosis/diagnostic imaging ; Thrombosis/epidemiology ; Thrombosis/etiology
Chemical Substances	Anticoagulants
Language	English
Publishing date	2022-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-07428-5
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Article ; Online: Influence of benign prostatic hyperplasia patterns detected with MRI on the clinical outcome after prostatic artery embolization.

Boschheidgen, Matthias / Al-Monajjed, Rouvier / Minko, Peter / Jannusch, Kai / Ullrich, Tim / Radke, Karl Ludger / Michalski, Rene / Radtke, Jan Philipp / Albers, Peter / Antoch, Gerald / Schimmöller, Lars

CVIR endovascular

2023 Volume 6, Issue 1, Page(s) 9

Abstract: Background: To investigate the influence of benign prostatic hyperplasia (BPH) patterns detected with MRI on clinical outcomes after prostatic artery embolization (PAE).: Materials & methods: This retrospective study included 71 consecutive patients ... ...

Abstract	Background: To investigate the influence of benign prostatic hyperplasia (BPH) patterns detected with MRI on clinical outcomes after prostatic artery embolization (PAE). Materials & methods: This retrospective study included 71 consecutive patients with lower urinary tract symptoms (LUTS), who underwent magnetic resonance imaging (MRI) of the prostate followed by PAE at a single centre. MRI scans were evaluated and BPH patterns were determined according to Wasserman type and a modified BPH classification. Additionally, scans were evaluated regarding the presence of adenomatous-dominant benign prostatic hyperplasia (AdBPH). LUTS were assessed using the International Prostate Symptom Score (IPSS) and urinary flow rate (Qmax). Follow-up examination included MRI and clinical outcome. Results: For clinical outcome at follow-up, IPSS showed median reduction of 54% (IQR 41-75%) and Qmax improved by 4.1 ml/s. We noted significant reduction in volume, intraprostatic protrusion, and prostatic urethral angle in our collective (p < 0.01). Median volume reduction was 25% (IQR 15%-34%). Bilateral embolization was a significant predictor for volume reduction at follow-up. Multiple linear regression analysis showed significant effect of high initial volume on reduction in IPSS after treatment (p < 0.01). Presence of AdBPH was significantly associated with both, volume loss and clinical improvement in terms of IPSS reduction (p < 0.01). Neither BPH pattern based on the Wassermann type nor modified BPH classification were significantly related with postinterventional IPSS and volume loss. Conclusions: Men benefit from PAE regardless the macroscopic BPH MRI pattern. Preinterventional prostate volume and presence of AdBPH on MRI should be considered for outcome prognosis after PAE.
Language	English
Publishing date	2023-03-02
Publishing country	Switzerland
Document type	Journal Article
ISSN	2520-8934
ISSN (online)	2520-8934
DOI	10.1186/s42155-023-00357-y
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Article ; Online: Resting Energy Expenditure in the Critically Ill and Healthy Elderly-A Retrospective Matched Cohort Study.

Lindner, Matthias / Geisler, Corinna / Rembarz, Kristina / Hummitzsch, Lars / Radke, David I / Schulte, Dominik M / Müller, Manfred J / Bosy-Westphal, Anja / Elke, Gunnar

Nutrients

2023 Volume 15, Issue 2

Abstract: The use of indirect calorimetry to measure resting energy expenditure (mREE) is widely recommended as opposed to calculating REE (cREE) by predictive equations (PE). The aim of this study was to compare mREE with cREE in critically ill, mechanically ... ...

Abstract	The use of indirect calorimetry to measure resting energy expenditure (mREE) is widely recommended as opposed to calculating REE (cREE) by predictive equations (PE). The aim of this study was to compare mREE with cREE in critically ill, mechanically ventilated patients aged ≥ 75 years and a healthy control group matched by age, gender and body mass index. The primary outcome was the PE accuracy rate of mREE/cREE, derived using Bland Altman plots. Secondary analyses included linear regression analyses for determinants of intraindividual mREE/cREE differences in the critically ill and interindividual mREE differences in the matched healthy cohort. In this retrospective study, 90 critically ill patients (median age 80 years) and 58 matched healthy persons were included. Median mREE was significantly higher in the critically ill (1457 kcal/d) versus the healthy cohort (1351 kcal/d), with low PE accuracy rates (21% to 49%). Independent predictors of mREE/cREE differences in the critically ill were body temperature, heart rate, FiO
MeSH term(s)	Aged ; Humans ; Aged, 80 and over ; Retrospective Studies ; Critical Illness ; Cohort Studies ; Predictive Value of Tests ; Energy Metabolism/physiology ; Calorimetry, Indirect ; Basal Metabolism/physiology
Language	English
Publishing date	2023-01-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15020303
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Article ; Online: The ElonginB/C-Cullin5-SOCS-Box-Complex Is a Potential Biomarker for Growth Hormone Disorders

Wilhelm Gossing / Lars Radke / Henrik Biering / Sven Diederich / Knut Mai / Marcus Frohme

Biomedicines, Vol 9, Iss 2, p

2021 Volume 201

Abstract	Insulin-like growth factor 1 (IGF-1) is the standard biochemical marker for the diagnosis and treatment control of acromegaly and growth hormone deficiency (GHD). However, its limitations necessitate the screening for new specific and sensitive biomarkers. The elonginB/C-cullin5-SOCS-box-complex (ECS-complex) (an intracellular five-protein complex) is stimulated by circulating growth hormone (GH) and regulates GH receptor levels through a negative feedback loop. It mediates the cells’ sensitivity for GH and therefore, represents a potent new biomarker for those diseases. In this study, individual ECS-complex proteins were measured in whole blood samples of patients with acromegaly (n = 32) or GHD (n = 12) via ELISA and compared to controls. Hierarchical clustering of the results revealed that by combining the three ECS-complex proteins suppressor of cytokine signaling 2 (SOCS2), cullin-5 and ring-box protein 2 (Rbx-2), 93% of patient samples could be separated from controls, despite many patients having a normal IGF-1 or not receiving medical treatment. SOCS2 showed the best individual diagnostic performance with an overall accuracy of 0.93, while the combination of the three proteins correctly identified all patients and controls. This resulted in perfect sensitivity and specificity for all patient groups, which demonstrates potential benefits of the ECS-complex proteins as clinical biomarkers for the diagnostics of GH-related diseases and substantiates their important role in GH metabolism.
Keywords	acromegaly ; growth hormone deficiency ; biomarker ; SOCS2 ; liquid biopsies ; pituitary ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Striated muscle-specific base editing enables correction of mutations causing dilated cardiomyopathy.

Grosch, Markus / Schraft, Laura / Chan, Adrian / Küchenhoff, Leonie / Rapti, Kleopatra / Ferreira, Anne-Maud / Kornienko, Julia / Li, Shengdi / Radke, Michael H / Krämer, Chiara / Clauder-Münster, Sandra / Perlas, Emerald / Backs, Johannes / Gotthardt, Michael / Dieterich, Christoph / van den Hoogenhof, Maarten M G / Grimm, Dirk / Steinmetz, Lars M

Nature communications

2023 Volume 14, Issue 1, Page(s) 3714

Abstract: Dilated cardiomyopathy is the second most common cause for heart failure with no cure except a high-risk heart transplantation. Approximately 30% of patients harbor heritable mutations which are amenable to CRISPR-based gene therapy. However, challenges ... ...

Abstract	Dilated cardiomyopathy is the second most common cause for heart failure with no cure except a high-risk heart transplantation. Approximately 30% of patients harbor heritable mutations which are amenable to CRISPR-based gene therapy. However, challenges related to delivery of the editing complex and off-target concerns hamper the broad applicability of CRISPR agents in the heart. We employ a combination of the viral vector AAVMYO with superior targeting specificity of heart muscle tissue and CRISPR base editors to repair patient mutations in the cardiac splice factor Rbm20, which cause aggressive dilated cardiomyopathy. Using optimized conditions, we repair >70% of cardiomyocytes in two Rbm20 knock-in mouse models that we have generated to serve as an in vivo platform of our editing strategy. Treatment of juvenile mice restores the localization defect of RBM20 in 75% of cells and splicing of RBM20 targets including TTN. Three months after injection, cardiac dilation and ejection fraction reach wild-type levels. Single-nuclei RNA sequencing uncovers restoration of the transcriptional profile across all major cardiac cell types and whole-genome sequencing reveals no evidence for aberrant off-target editing. Our study highlights the potential of base editors combined with AAVMYO to achieve gene repair for treatment of hereditary cardiac diseases.
MeSH term(s)	Mice ; Animals ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Dilated/therapy ; Cardiomyopathy, Dilated/metabolism ; Gene Editing ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Myocardium/metabolism ; Mutation ; Myocytes, Cardiac/metabolism
Chemical Substances	RNA-Binding Proteins ; RBM20 protein, mouse
Language	English
Publishing date	2023-06-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-39352-1
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