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Article ; Online: Of Pea Plants and Platelets.

Desch, Karl C

2020 Volume 127, Issue 9, Page(s) 1195–1197

MeSH term(s)	Biomarkers ; Blood Platelets ; Genomics ; Pisum sativum ; Thromboembolism
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-10-08
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.120.318002
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Article: Regulation of plasma von Willebrand factor.

Desch, Karl C

F1000Research

2018 Volume 7, Page(s) 96

Abstract: Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet ... ...

Abstract	Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.
Language	English
Publishing date	2018-01-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2699932-8
ISSN	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.13056.1
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Article ; Online: Dissecting the genetic determinants of hemostasis and thrombosis.

Desch, Karl C

Current opinion in hematology

2015 Volume 22, Issue 5, Page(s) 428–436

Abstract: Purpose of review: New DNA genotyping and sequencing technologies have facilitated the rapid advancement in our knowledge of human genomic variation and a search for the heritable determinants of complex genetic traits. This review highlights findings ... ...

Abstract	Purpose of review: New DNA genotyping and sequencing technologies have facilitated the rapid advancement in our knowledge of human genomic variation and a search for the heritable determinants of complex genetic traits. This review highlights findings from recent genetic studies of complex traits primarily related to venous thromboembolism and provides tools to understand and interpret genome-wide association studies and next-generation sequencing studies. Recent findings: Genome-wide studies of venous thromboembolic disease and the variation of the protein components of the hemostatic system have been reported. The results of these studies have suggested that variants in a diverse set of known and new genes contribute to the heritability of these traits, but that many of the genetic determinants of these traits still remain undiscovered. Summary: Next-generation sequencing studies and functional studies of the gene loci that contribute to hemostatic traits are currently underway. Future studies that explore the role of rare genetic variants, regulatory elements of the genome and gene-gene interactions will be required for a more complete understanding of the genetic control of the hemostatic system and for the application of this knowledge to the care of patients with disorders of thrombosis and hemostasis.
MeSH term(s)	Epistasis, Genetic ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Genome-Wide Association Study ; Genomics ; Hemostasis/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Sequence Analysis, DNA/methods ; Venous Thrombosis/genetics
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000165
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Regulation of plasma von Willebrand factor [version 1; referees

Karl C Desch

F1000Research, Vol

3 approved]

2018 Volume 7

Abstract	Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.
Keywords	Medicine ; R ; Science ; Q
Subject code	306
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 6- and 12-Month Follow-Up From a Randomized Clinical Trial of Ultrasound vs Radiofrequency Renal Denervation (RADIOSOUND-HTN).

Fengler, Karl / Rommel, Karl-Philipp / Kriese, Wenzel / Blazek, Stephan / Besler, Christian / von Roeder, Maximilian / Desch, Steffen / Thiele, Holger / Lurz, Philipp

JACC. Cardiovascular interventions

2023 Volume 16, Issue 3, Page(s) 367–369

MeSH term(s)	Humans ; Follow-Up Studies ; Treatment Outcome ; Kidney ; Hypertension/surgery ; Hypertension/drug therapy ; Denervation ; Sympathectomy/adverse effects ; Blood Pressure ; Antihypertensive Agents/therapeutic use
Chemical Substances	Antihypertensive Agents
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Randomized Controlled Trial ; Letter
ZDB-ID	2452157-7
ISSN	1876-7605 ; 1936-8798
ISSN (online)	1876-7605
ISSN	1936-8798
DOI	10.1016/j.jcin.2022.10.058
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Article ; Online: Von Willebrand Factor and ADAMTS13: Too Much or Too Little of a Good Thing?

Emmer, Brian T / Ginsburg, David / Desch, Karl C

Arteriosclerosis, thrombosis, and vascular biology

2016 Volume 36, Issue 12, Page(s) 2281–2282

MeSH term(s)	ADAMTS13 Protein ; von Willebrand Factor
Chemical Substances	von Willebrand Factor ; ADAMTS13 Protein (EC 3.4.24.87)
Language	English
Publishing date	2016-11-22
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.116.308531
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Article ; Online: GLP-1 in patients with myocardial infarction complicated by cardiogenic shock-an IABP-SHOCK II-substudy.

Lehrke, Michael / Fuernau, Georg / Jung, Christian / Kahles, Florian / Moellmann, Julia / Eitel, Ingo / Thelemann, Nathalie / Desch, Steffen / Werdan, Karl / Zeymer, Uwe / Adams, Volker / Marx, Nikolaus / Thiele, Holger

Clinical research in cardiology : official journal of the German Cardiac Society

2024

Abstract: Background: Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted in response to nutritional and inflammatory stimuli. Elevated GLP-1 levels predict adverse outcome in patients with acute myocardial infarction or sepsis. GLP-1 holds ... ...

Abstract	Background: Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted in response to nutritional and inflammatory stimuli. Elevated GLP-1 levels predict adverse outcome in patients with acute myocardial infarction or sepsis. GLP-1 holds cardioprotective effects and GLP-1 receptor agonists reduce cardiovascular events in high-risk patients with diabetes. In this study, we aimed to investigate the capacity of GLP-1 to predict outcome in patients with cardiogenic shock (CS) complicating myocardial infarction. Methods: Circulating GLP-1 levels were serially assessed in 172 individuals during index PCI and day 2 in a prospectively planned biomarker substudy of the IABP-SHOCK II trial. All-cause mortality at short- (30 days), intermediate- (1 year), and long-term (6 years) follow-up was used for outcome assessment. Results: Patients with fatal short-term outcome (n = 70) exhibited higher GLP-1 levels [86 (interquartile range 45-130) pM] at ICU admission in comparison to patients with 30-day survival [48 (interquartile range 33-78) pM; p < 0.001] (n = 102). Repeated measures ANOVA revealed a significant interaction of GLP-1 dynamics from baseline to day 2 between survivors and non-survivors (p = 0.04). GLP-1 levels above vs. below the median proved to be predictive for short- [hazard ratio (HR) 2.43; 95% confidence interval (CI) 1.50-3.94; p < 0.001], intermediate- [HR 2.46; 95% CI 1.62-3.76; p < 0.001] and long-term [HR 2.12; 95% CI 1.44-3.11; p < 0.001] outcome by multivariate Cox-regression analysis. Conclusion: Elevated plasma levels of GLP-1 are an independent predictor for impaired prognosis in patients with myocardial infarction complicated by CS. The functional relevance of GLP-1 in this context is currently unknown and needs further investigations. Trial registration: www. Clinicaltrials: gov Identifier: NCT00491036.
Language	English
Publishing date	2024-01-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2213295-8
ISSN	1861-0692 ; 1861-0684
ISSN (online)	1861-0692
ISSN	1861-0684
DOI	10.1007/s00392-023-02366-2
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Article ; Online: Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study.

Desch, Michael / Schlecker, Christina / Hohl, Kathrin / Liesenfeld, Karl-Heinz / Chan, Tom / Müller, Fabian / Wunderlich, Glen / Keller, Sascha / Ishiguro, Naoki / Wind, Sven

Journal of clinical psychopharmacology

2023 Volume 43, Issue 2, Page(s) 113–121

Abstract: Purpose/background: Glycine transporter-1 inhibitors may ameliorate cognitive deficits in schizophrenia. This study evaluated potential drug-drug interactions with the glycine transporter-1 inhibitor BI 425809.: Methods/procedures: Interactions with ... ...

Abstract	Purpose/background: Glycine transporter-1 inhibitors may ameliorate cognitive deficits in schizophrenia. This study evaluated potential drug-drug interactions with the glycine transporter-1 inhibitor BI 425809. Methods/procedures: Interactions with cytochromes P450 (CYP) and P-glycoprotein (P-gp) were assessed in in vitro assays using human hepatocytes and Caco-2 cells, respectively. Pharmacokinetic characteristics of probe drugs were subsequently assessed in a Phase I, open-label, single-sequence crossover study in healthy male participants. Participants received a probe-drug cocktail containing midazolam (CYP3A4), warfarin (CYP2C9), and omeprazole (CYP2C19) and a separate dose of digoxin (P-gp), alone and on a background of steady-state BI 425809 25 mg once daily in 2 treatment periods. Adverse events were monitored. Findings/results: In vitro assays revealed concentration-dependent induction of CYP3A4 and inhibition of P-gp by BI 425809. In the clinical study, 12 of 13 participants completed both periods. With BI 425809, area under the plasma concentration curve from administration to the last measurement (AUC 0-tz ) and maximum plasma concentration ( Cmax ) for midazolam were lower than when administered alone. Adjusted geometric mean ratios (90% confidence interval) were 70.6% (63.9%-78.1%) for AUC 0-tz and 77.6% (67.3%-89.4%) for Cmax . For warfarin and digoxin, AUC 0-tz and Cmax were similar with and without BI 425809. For omeprazole, BI 425809 slightly reduced AUC 0-tz but not Cmax versus omeprazole alone. No new safety signals were identified. Implications/conclusions: These findings indicate induction of CYP3A4 by once-daily BI 425809 25 mg (the assumed highest therapeutic dose) and no meaningful effects on CYP2C9, CYP2C19, or P-gp in vivo.
MeSH term(s)	Humans ; Male ; Glycine Plasma Membrane Transport Proteins ; Midazolam ; Cytochrome P-450 CYP2C19 ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Cytochrome P-450 CYP3A ; Warfarin ; Cross-Over Studies ; Cytochrome P-450 CYP2C9 ; Caco-2 Cells ; Caffeine/pharmacokinetics ; Drug Interactions ; Cytochrome P-450 Enzyme System/metabolism ; Omeprazole/pharmacokinetics ; ATP Binding Cassette Transporter, Subfamily B ; Digoxin/pharmacokinetics ; Area Under Curve
Chemical Substances	Glycine Plasma Membrane Transport Proteins ; Midazolam (R60L0SM5BC) ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1) ; BI 425809 ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Warfarin (5Q7ZVV76EI) ; Cytochrome P-450 CYP2C9 (EC 1.14.13.-) ; Caffeine (3G6A5W338E) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Omeprazole (KG60484QX9) ; ATP Binding Cassette Transporter, Subfamily B ; Digoxin (73K4184T59)
Language	English
Publishing date	2023-01-26
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	604631-9
ISSN	1533-712X ; 0271-0749
ISSN (online)	1533-712X
ISSN	0271-0749
DOI	10.1097/JCP.0000000000001656
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Article ; Online: Assessment of arterial stiffness to predict blood pressure response to renal sympathetic denervation.

Fengler, Karl / Rommel, Karl-Philipp / Kriese, Wenzel / Kresoja, Karl-Patrik / Blazek, Stephan / Obradovic, Danilo / Feistritzer, Hans-Josef / Lücke, Christian / Gutberlet, Matthias / Desch, Steffen / Thiele, Holger / Lurz, Philipp

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology

2022 Volume 18, Issue 8, Page(s) e686–e694

Abstract: Background: Recent trials support the efficacy of renal sympathetic denervation (RDN) to reduce blood pressure (BP). Nevertheless, about one third of patients are considered non-responders to RDN. Previous retrospective analyses suggest arterial ... ...

Abstract	Background: Recent trials support the efficacy of renal sympathetic denervation (RDN) to reduce blood pressure (BP). Nevertheless, about one third of patients are considered non-responders to RDN. Previous retrospective analyses suggest arterial stiffness could predict BP response to RDN. Aims: We prospectively assessed the potential of invasive pulse wave velocity (iPWV) to predict BP response to RDN. Additionally, we aimed to establish non-invasive models based on arterial stiffness to predict BP response to RDN. Methods: iPWV, magnetic resonance imaging-based markers of arterial stiffness and the carotid-femoral pulse wave velocity were recorded prior to RDN in patients with treatment resistant hypertension. Changes in daytime BP after 3 months were analysed according to the prespecified iPWV cut-off (14.4 m/s). Regression analyses were used to establish models for non-invasive prediction of BP response. Results were compared to iPWV as reference and were then validated in an external patient cohort. Results: Eighty patients underwent stiffness assessment before RDN. After 3 months, systolic 24h and daytime BP were reduced by 13.6±9.8 mmHg and 14.7±10.6 mmHg in patients with low iPWV, versus 6.2±13.3 mmHg and 6.3±12.8 mmHg in those with high iPWV (p<0.001 for both). Upon regression analysis, logarithmic ascending aortic distensibility and systolic baseline BP independently predicted BP change at follow-up. Both were confirmed in the validation cohort. Conclusions: iPWV is an independent predictor for BP response after RDN. In addition, BP change prediction following RDN using non-invasive measures is feasible. This could facilitate patient selection for RDN treatment.
MeSH term(s)	Blood Pressure/physiology ; Denervation ; Humans ; Hypertension ; Kidney/surgery ; Pulse Wave Analysis ; Retrospective Studies ; Sympathectomy/methods ; Treatment Outcome ; Vascular Stiffness/physiology
Language	English
Publishing date	2022-10-07
Publishing country	France
Document type	Journal Article
ZDB-ID	2457174-X
ISSN	1969-6213 ; 1774-024X
ISSN (online)	1969-6213
ISSN	1774-024X
DOI	10.4244/EIJ-D-21-01036
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Article ; Online: Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress.

Kahn, Susan R / Arnold, Donald M / Casari, Caterina / Desch, Karl C / Devreese, Katrien M J / Favaloro, Emmanuel J / Gaertner, Florian / Gouw, Samantha C / Gresele, Paolo / Griffioen, Arjan W / Heger, Lukas / Kini, R Manjunatha / Kohli, Shrey / Leader, Avi / Lisman, Ton / Lordkipanidzé, Marie / Mullins, Eric / Okoye, Helen Chioma / Rosovsky, Rachel P /

Salles-Crawley, Isabelle I / Selby, Rita / Sholzberg, Michelle / Stegner, David / Violi, Francesco / Weyand, Angela C / Williams, Suzan / Zheng, Ze

Research and practice in thrombosis and haemostasis

2023 Volume 7, Issue 4, Page(s) 100193

Abstract: This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) took place in person in Montréal, Canada, from June 24-28, 2023. The conference, held annually, highlighted cutting-edge advances in basic, translational, population ... ...

Abstract	This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) took place in person in Montréal, Canada, from June 24-28, 2023. The conference, held annually, highlighted cutting-edge advances in basic, translational, population and clinical sciences relevant to the Society. As for all ISTH congresses, we offered a special, congress-specific scientific theme; this year, the special theme was immunothrombosis. Certainly, over the last few years, COVID-19 infection and its related thrombotic and other complications have renewed interest in the concepts of thromboinflammation and immunothrombosis; namely, the relationship between inflammation, infection and clotting. Other main scientific themes of the Congress included Arterial Thromboembolism, Coagulation and Natural Anticoagulants, Diagnostics and Omics, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostatic System in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. Among other sessions, the program included 28 State-of-the-Art (SOA) sessions with a total of 84 talks given by internationally recognized leaders in the field. SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the Congress.
Language	English
Publishing date	2023-06-21
Publishing country	United States
Document type	Journal Article
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1016/j.rpth.2023.100193
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