| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
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| 3. |
- Hahn, Rebecca T, et al.
(författare)
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Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.
- 2023
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Ingår i: Journal of the American College of Cardiology. - 1558-3597.
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Tidskriftsartikel (refereegranskat)abstract
- Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.
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| 4. |
- Hahn, Rebecca T, et al.
(författare)
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Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.
- 2023
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Ingår i: The Annals of thoracic surgery. - 1552-6259.
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Tidskriftsartikel (refereegranskat)abstract
- Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.
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| 5. |
- Hahn, Rebecca T, et al.
(författare)
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Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.
- 2023
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Ingår i: European heart journal. - 1522-9645.
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Tidskriftsartikel (refereegranskat)abstract
- Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.
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| 6. |
- Kappetein, Arie Pieter, et al.
(författare)
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Design and rationale for a randomised comparison of everolimus-eluting stents and coronary artery bypass graft surgery in selected patients with left main coronary artery disease : the EXCEL trial
- 2016
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Ingår i: EuroIntervention. - 1774-024X .- 1969-6213. ; 12:7, s. 861-872
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Coronary artery bypass graft (CABG) surgery is the standard of care for revascularisation of patients with left main coronary artery disease (LMCAD). Recent studies have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may provide comparable outcomes in selected patients with LMCAD without extensive CAD. We therefore designed a trial to investigate whether PCI with XIENCE cobalt-chromium everolimus-eluting stents (CoCr-EES) would result in non-inferior or superior clinical outcomes to CABG in selected patients with LMCAD. Methods and results: The Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is a prospective, open-label, multicentre, international study of 1,900 randomised subjects. Patients with significant LMCAD with a SYNTAX score <= 32 and local Heart Team consensus that the subject is appropriate for revascularisation by both PCI and CABG are consented and randomised 1:1 to undergo PCI using CoCr-EES or CABG. All patients undergo follow-up for five years. The primary endpoint is the three-year composite rate of death, stroke or myocardial infarction, assessed at a median follow-up of at least three years (with at least two-year follow-up in all patients), powered for sequential non-inferiority and superiority testing. Conclusions: The EXCEL study will define the contemporary roles of CABG and PCI using XIENCE CoCr-EES in patients with LMCAD disease with low and intermediate SYNTAX scores.
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| 7. |
- Neiman, Daniel, et al.
(författare)
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Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells
- 2020
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that unmethylated insulin promoter fragments in plasma derive exclusively from β cells, reflect their recent demise, and can be used to assess β cell damage in type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a β cell–specific DNA methylation signature, by simultaneous assessment of 6 DNA methylation markers, that identifies β cell DNA in mixtures containing as little as 0.03% β cell DNA (less than 1 β cell genome equivalent). Based on this assay, plasma from nondiabetic individuals (N = 218, aged 4–78 years) contained on average only 1 β cell genome equivalent/mL. As expected, cell-free DNA (cfDNA) from β cells was significantly elevated in islet transplant recipients shortly after transplantation. We also detected β cell cfDNA in a patient with KATP congenital hyperinsulinism, in which substantial β cell turnover is thought to occur. Strikingly, in contrast to previous reports, we observed no elevation of β cell–derived cfDNA in autoantibody-positive subjects at risk for type 1 diabetes (N = 32), individuals with recent-onset type 1 diabetes (<4 months, N = 92), or those with long-standing disease (>4 months, N = 38). We discuss the utility of sensitive β cell cfDNA analysis and potential explanations for the lack of a β cell cfDNA signal in type 1 diabetes.
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| 8. |
- Segal, Eran, et al.
(författare)
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Building an international consortium for tracking coronavirus health status
- 2020
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26:8, s. 1161-1165
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We call upon the research community to standardize efforts to use daily self-reported data about COVID-19 symptoms in the response to the pandemic and to form a collaborative consortium to maximize global gain while protecting participant privacy.
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| 9. |
- Shahim, Bahira, et al.
(författare)
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Impact of Peripheral Artery Disease in Patients With Heart Failure Undergoing Transcatheter Mitral Valve Repair: The COAPT Trial.
- 2023
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Ingår i: Journal of the American Heart Association. - 2047-9980.
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Tidskriftsartikel (refereegranskat)abstract
- Background Peripheral artery disease (PAD) and heart failure (HF) often coexist. Whether PAD influences outcomes of transcatheter mitral valve repair (TMVr) in patients with HF and severe secondary mitral regurgitation is unknown. The objectives are to assess the impact of PAD on outcomes of TMVr plus guideline-directed medical therapy (GDMT) versus GDMT alone in patients with HF and secondary mitral regurgitation. Methods and Results The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized patients with HF with ≥moderate-to-severe secondary mitral regurgitation to TMVr with MitraClip implant plus GDMT versus GDMT alone. We evaluated the relationship between PAD and 2-year outcomes in the COAPT trial and examined whether PAD modified the benefits of TMVr. Among 614 patients enrolled, 109 (17.8%) had PAD. By multivariable analysis, PAD was independently associated with 2-year mortality (adjusted hazard ratio [adjHR], 1.51 [95% CI, 1.07-2.15]) but not HF hospitalizations. Compared with GDMT alone, TMVr reduced the 2-year risk of death in patients without PAD (adjHR, 0.42 [95% CI, 0.30-0.60]) but not those with PAD (adjHR, 1.27 [95% CI, 0.72-2.27]; Pinteraction=0.001). In contrast, TMVr reduced HF hospitalizations consistently in patients with (adjHR, 0.65 [95% CI, 0.35-1.23]) and without (adjHR, 0.42 [95% CI, 0.31-0.57]) PAD (Pinteraction=0.22). Improvements in health status and exercise capacity at 2 years with TMVr compared with GDMT alone were similar in degree, irrespective of PAD status (Pinteraction=0.76 and 0.64, respectively). Conclusions In patients with HF and severe secondary mitral regurgitation, the reduced mortality with TMVr in the overall COAPT study population was not observed in the subgroup of patients with PAD. However, TMVr reduced HF hospitalizations and improved health status and exercise capacity consistently in patients with and without PAD. Registration Clinical Trial Name: Cardiovascular Outocmes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (The COAPT Trial); URL: https://www.clinicaltrials.gov/; Unique identifier: NCT01626079. https://clinicaltrials.gov/ct2/show/NCT01626079.
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