Joint Associations Between Body Mass Index and Waist Circumference With Atrial Fibrillation in Men and Women.

Background Associations between adiposity and atrial fibrillation (AF) might differ between sexes. We aimed to determine precise estimates of the risk of AF by body mass index (BMI) and waist circumference (WC) in men and women. Methods and Results Between 2008 and 2013, over 3.

Caging the dragon: Research approach to COVID-19-related thrombosis.

The incidence of venous thrombosis, mostly pulmonary embolism (PE), ranging from local immunothrombosis to central emboli, but also deep vein thrombosis (DVT) in people with coronavirus disease 2019 (COVID-19) is reported to be remarkably high. The relevance of better understanding, predicting, treating, and preventing COVID-19-associated venous thrombosis meets broad support, as can be concluded from the high number of research, review, and guideline papers that have been published on this topic. The Dutch COVID & Thrombosis Coalition (DCTC) is a multidisciplinary team involving a large number of Dutch experts in the broad area of venous thrombosis and hemostasis research, combined with experts on virology, critically ill patients, pulmonary diseases, and community medicine, across all university hospitals and many community hospitals in the Netherlands.

Automatic quantification of lymphocyte vacuolization in peripheral blood smears of patients with Batten's disease (CLN3 disease).

Quantifying lymphocyte vacuolization in peripheral blood smears (PBSs) serves as a measure for disease severity in CLN3 disease-a lysosomal storage disorder of childhood-onset. However, thus far quantification methods are based on labor-intensive manual assessment of PBSs. As machine learning techniques like convolutional neural networks (CNNs) have been deployed quite successfully in detecting pathological features in PBSs, we explored whether these techniques could be utilized to automate quantification of lymphocyte vacuolization.

Associations Between Blood Biomarkers, Cardiac Function, and Adverse Outcome in a Young Fontan Cohort.

Background Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a young cohort who have undergone the Fontan procedure. Methods and Results In multicenter prospective studies patients who have undergone the Fontan procedure underwent blood sampling, cardiopulmonary exercise testing, and stress cardiac magnetic resonance imaging.

Clinical Course Long After Atrial Switch: A Novel Risk Score for Major Clinical Events.

Background Patients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but data on the emerging risks remain scarce. We assessed the risk for events during the clinical course in adulthood, and provided a novel risk score for event-free survival. Methods and Results This multicenter study observed 167 patients with transposition of the great arteries corrected by an atrial switch operation (61% Mustard procedure; age, 28 [interquartile range, 24-36] years) for 13 (interquartile range, 9-16) years, during which 16 (10%) patients died, 33 (20%) had HF events, defined as HF hospitalizations, heart transplantation, ventricular assist device implantation, or HF-related death, and 15 (9%) had symptomatic ventricular arrhythmias.

The association of circulating amylin with β-amyloid in familial Alzheimer's disease.

Introduction: This study assessed the hypothesis that circulating human amylin (amyloid-forming) cross-seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods: Evidence of amylin-AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non-APP/PS1 rats.

Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission.

Background Detailed insights in temporal evolution of high-sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post-ACS kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT), and to determine their intra- and interindividual variation in clinically stable patients. Methods and Results We determined hs-cTnI (Abbott) and hs-cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1-year follow-up.

Quantitative multiplex profiling of the complement system to diagnose complement-mediated diseases.

Objectives: Complement deficiencies are difficult to diagnose because of the variability of symptoms and the complexity of the diagnostic process. Here, we applied a novel 'complementomics' approach to study the impact of various complement deficiencies on circulating complement levels.

Methods: Using a quantitative multiplex mass spectrometry assay, we analysed 44 peptides to profile 34 complement proteins simultaneously in 40 healthy controls and 83 individuals with a diagnosed deficiency or a potential pathogenic variant in 14 different complement proteins.

Associations of Observational and Genetically Determined Caffeine Intake With Coronary Artery Disease and Diabetes Mellitus.

Background Caffeine is the most widely consumed psychostimulant and is associated with lower risk of coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). However, whether these associations are causal remains unknown. This study aimed to identify genetic variants associated with caffeine intake, and to investigate evidence for causal links with CAD or T2DM.

Short-Term Variability of the QT Interval Can be Used for the Prediction of Imminent Ventricular Arrhythmias in Patients With Primary Prophylactic Implantable Cardioverter Defibrillators.

Background Short-term variability of the QT interval (STV) has been proposed as a novel electrophysiological marker for the prediction of imminent ventricular arrhythmias in animal models. Our aim is to study whether STV can predict imminent ventricular arrhythmias in patients. Methods and Results In 2331 patients with primary prophylactic implantable cardioverter defibrillators, 24-hour ECG Holter recordings were obtained as part of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators) study.

Neonatal carnitine concentrations in relation to gestational age and weight.

Background: Free carnitine has been measured in the Dutch newborn screening (NBS) program since 2007 with a referral threshold of ≤5 μmol/L, regardless of gestational age or birthweight. However, several studies suggest that carnitine concentrations may depend on gestational age and birthweight. We evaluated differences in postnatal day-to-day carnitine concentrations in newborns based on gestational age (GA) and/or weight for GA (WfGA).

Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27-year-long longitudinal study.

Objectives: Cytomegalovirus infection is thought to affect the immune system and to impact general health during ageing. Higher CMV-specific antibody levels in the elderly are generally assumed to reflect experienced viral reactivation during life. Furthermore, high levels of terminally differentiated and CMV-specific T cells are hallmarks of CMV infection, which are thought to expand over time, a process also referred to as memory inflation.

Emerging insights on the role of gasdermins in infection and inflammatory diseases.

The gasdermins, family of pore-forming proteins, are emerging key regulators of infection, autoinflammation and antitumor immunity. Multiple studies have recently characterised their crucial roles in driving pyroptosis, a lytic pro-inflammatory type of cell death. Additionally, gasdermins also act as key effectors of NETosis, secondary necrosis and apoptosis.

Proinflammatory intervertebral disc cell and organ culture models induced by tumor necrosis factor alpha.

Inflammation plays an important role in the pathogenesis of intervertebral disc (IVD) degeneration. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) has shown markedly higher expression in degenerated human disc tissue compared with healthy controls. Anti-inflammatory treatment targeting TNF-α has shown to alleviate discogenic pain in patients with low back pain.

Cerebral blood flow and cognitive functioning in patients with disorders along the heart-brain axis: Cerebral blood flow and the heart-brain axis.

Introduction: We examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI]).

Methods: We included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi-center Heart-Brain Study. We used pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF.

Sex differences in memory clinic patients with possible vascular cognitive impairment.

Introduction: We aimed to establish sex differences in vascular brain damage of memory clinic patients with possible vascular cognitive impairment (VCI).

Methods: A total of 860 memory clinic patients (aged 67.7 ± 8.

Velocity Pulsatility and Arterial Distensibility Along the Internal Carotid Artery.

Background Attenuation of velocity pulsatility along the internal carotid artery (ICA) is deemed necessary to protect the microvasculature of the brain. The role of the carotid siphon within the whole ICA trajectory in pulsatility attenuation is still poorly understood. This study aims to assess arterial variances in velocity pulsatility and distensibility over the whole ICA trajectory, including effects of age and sex.

Semantic loss marks early Alzheimer's disease-related neurodegeneration in older adults without dementia.

Objective: To assess progression of semantic loss in early stages of cognitive decline using semantic and letter fluency performance, and its relation with Alzheimer's disease (AD)-specific neurodegeneration using longitudinal multimodal neuroimaging measures.

Methods: Change in verbal fluency was analyzed among 2261 non-demented individuals with a follow-up diagnosis of no mild cognitive impairment (MCI), amnestic MCI (aMCI), non-amnestic MCI (naMCI), or incident dementia, using linear mixed models across 4 years of follow-up, and relations with magnetic resonance imaging (MRI; n = 1536) and F-fluorodeoxyglucose brain positron emission tomography (F-FDG-PET) imaging (n = 756) using linear regression models across 2 years of follow-up.

Results: Semantic fluency declined-fastest in those at higher risk for AD (apolipoprotein E [APOE] e4 carriers, Clinical Dementia Rating score of .

Small vessel disease lesion type and brain atrophy: The role of co-occurring amyloid.

Introduction: It is unknown whether different types of small vessel disease (SVD), differentially relate to brain atrophy and if co-occurring Alzheimer's disease pathology affects this relation.

Methods: In 725 memory clinic patients with SVD (mean age 67 ± 8 years, 48% female) we compared brain volumes of those with moderate/severe white matter hyperintensities (WMHs; n = 326), lacunes (n = 132) and cerebral microbleeds (n = 321) to a reference group with mild WMHs (n = 197), also considering cerebrospinal fluid (CSF) amyloid status in a subset of patients (n = 488).

Results: WMHs and lacunes, but not cerebral microbleeds, were associated with smaller gray matter (GM) volumes.

Sex differences in flow cytometry-based platelet reactivity in stable outpatients suspected of myocardial ischemia.

Background: Antiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet therapies is unclear.

Evaluation of 11 years of newborn screening for maple syrup urine disease in the Netherlands and a systematic review of the literature: Strategies for optimization.

Maple syrup urine disease (MSUD) leads to severe neurological deterioration unless diagnosed early and treated immediately. We have evaluated the effectiveness of 11 years of MSUD newborn screening (NBS) in the Netherlands (screening >72 hours, referral if both total leucine (Xle) and valine ≥400 μmol/L blood) and have explored possibilities for improvement by combining our data with a systematic literature review and data from Collaborative Laboratory Integrated Reports (CLIR). Dutch MSUD NBS characteristics and accuracy were determined.

A feasibility study of implementing a patient-centered outcome set for pregnancy and childbirth.

Background And Aims: Patient-reported outcome and experience measures (PROM and PREM) can facilitate shared decision making and hold potential to improve healthcare quality. However, their adoption in perinatal care is still limited. The International Consortium for Health Outcomes Measurement (ICHOM) developed a Pregnancy and Childbirth (PCB) outcome set, including PROM and PREM questionnaires.

Clinical outcomes in hemophilia: Towards development of a core set of standardized outcome measures for research.

Introduction: A lack of uniformity in the choice of outcome measurement in hemophilia care and research has led to studies with incomparable results. We identified a need to define core outcome measures for use in research and clinical care of persons with hemophilia.

Objective: To move toward a core set of outcome measures for the assessment of persons with hemophilia in research and practice.