Rigshospitalet (meaning The National, State or Hospital of the Realm, but not usually translated) is the largest hospital in Denmark and the most highly specialised hospital in the country. The hospital's main building is a 16-storey functionalist highrise, one of the tallest structures in the central parts of the city. Rigshospitalet neighbours the Panum Building which houses the Faculty of Health and Medical Sciences at the University of Copenhagen. As a teaching hospital it is part of the framework organisation Copenhagen University Hospital.
Cardiac involvement is increasingly recognized in women carrying pathogenic variants in the dystrophin (DMD) gene, both Duchenne and Becker-associated, but the long-term natural history of cardiac structure, function, and conduction abnormalities in this group is not well understood. We conducted a prospective 7-year follow-up study to investigate the evolution of ventricular function, myocardial fibrosis, and arrhythmias. 34 women with confirmed pathogenic DMD gene variants (19 predicted to cause Duchenne muscular dystrophy and 15 Becker muscular dystrophy) underwent assessments after a mean of 7 years. Evaluations included cardiac magnetic resonance imaging with late gadolinium enhancement, 24-h Holter monitoring, 12-lead electrocardiography (ECG), cardiac biomarkers, and clinical examinations. At the group level, left ventricular ejection fraction (LVEF) remained stable over follow-up (p = 0.403). Six women had a ≥ 5
It remains undetermined whether gastrointestinal bleeding (GIB) associated with direct oral anticoagulant (DOAC) or vitamin K antagonists (VKA) is more severe. In Danish nationwide registries, we identified patients with atrial fibrillation (AF) treated with anticoagulation with gastrointestinal bleeding (GIB). Logistic regression models were used to compare GIB severity between DOAC and VKA users, defined by 1. red blood cell transfusion or in-hospital death and 2. endoscopies. From 2012–2018, 6,784 anticoagulated AF patients with GIB were identified; 3,724 patients VKA users and 3,060 DOAC (apixaban, dabigatran or rivaroxaban) users. The proportion of upper GIB was 49
Understanding the durability of faricimab with three monthly loading injections in a real-world clinical setting is important for optimizing treatment intervals and reducing the treatment burden. The aim of this study was to evaluate the durability and visual outcomes of a loading dose regimen consisting of three consecutive monthly faricimab injections in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). This is a retrospective, single-center cohort study using chart review and an electronic injection database, including treatment-naïve patients with nAMD aged 50 years or older who received three monthly faricimab injections between 1 November 2023 and 31 August 2024. Overall, 827 eyes of 742 patients were included in the study. Following the loading dose, the median injection-free interval was 15.0 weeks (95
RATIONALE:Chronic mucus hypersecretion contributes to airway obstruction in asthma. OBJECTIVES:To assess dupilumab efficacy by baseline mucus plug score. METHODS:In VESTIGE (NCT04400318), adults with moderate-to-severe asthma, baseline blood eosinophils ≥300 cells/μL, and fractional exhaled nitric oxide (FeNO) ≥25 ppb received dupilumab 300 mg (n = 72) or placebo (n = 37) every 2 weeks for 24 weeks. Post hoc analyses included mucus plug score change from baseline, and patient proportion achieving FeNO <25 ppb, percent predicted FEV1, and FVC stratified by baseline mucus plug score (high/low defined by score ≥4 or 0-3.5, respectively, derived from high-resolution computed tomography scans). MEASUREMENTS AND MAIN RESULTS:Fewer dupilumab-receiving patients had high mucus plug score at week 24 than at baseline (32.8% vs 67.2%); proportions remained similar in placebo-receiving patients (76.7% vs 73.3%). Dupilumab versus placebo recipients were more likely to achieve FeNO <25 ppb in high-/low-mucus-plug score subgroups (odds ratio, 6.64; P = .003/8.54; P = .024). Dupilumab versus placebo significantly increased pre-/post-bronchodilator percent predicted FEV1 (least squares mean difference [LSMD], 16.77 percentage points [95% CI, 9.81-23.73]; P <.0001 [pre] and 12.70 [95% CI, 3.87-21.52]; P = .0055 [post]) and pre-bronchodilator FVC (LSMD, 0.42 mL [95% CI, 0.17-0.66]; P = .001), and numerically improved post-bronchodilator FVC (LSMD, 0.30 mL [95% CI, 0.01-0.59]; P = .0399) in the high-mucus-plug score subgroup. CONCLUSIONS:Dupilumab reduced mucus plug scores and improved lung function in patients with moderate-to-severe asthma with high baseline mucus plug score, and increased the likelihood of achieving FeNO <25 ppb regardless of baseline mucus plug score.
Rare genetic factors have been shown to substantially contribute to mental illness, but so far, no precision treatments for mental disorders have been described. It was recently identified that rare variants in GRIN2A encoding the GluN2A subunit of the N-methyl-D-aspartate receptor (NMDAR) confer a substantial risk for schizophrenia. To determine the prevalence of mental disorders among individuals with GRIN2A-related disorders, we enquired the presence of psychiatric symptoms in 235 individuals with pathogenic variants in GRIN2A who had previously enrolled in our global GRIN registry. We identified null variants in GRIN2A (GRIN2Anull) to be significantly associated with a broad spectrum of mental disorders including schizophrenia compared to a longitudinal population cohort (FinRegistry) as well as missense variants (GRIN2Amissense). In our cohort, GRIN2Anull-related mental disorders manifest in early childhood or adolescence, which is substantially earlier than the average adult onset in the general population. In 68% of co-incident epilepsy and mental disorder, mental disorders start after epilepsy offset and the age of epilepsy offset correlated with mental disorder onset. GRIN2Anull-related phenotypes appear to occasionally even manifest as isolated mental disorder, i.e. as schizophrenia or mood disorder without further GRIN2A-specific symptoms, such as intellectual disability and/or epilepsy. As L-serine is known to mediate co-agonistic effects on the NMDAR, we applied it to four individuals with GRIN2Anull-related mental disorders, all of whom experienced improvements of their neuropsychiatric phenotype. GRIN2Anull appears to be the first monogenic cause of early-onset and even isolated mental disorders, such as early-onset schizophrenia. Genetic testing should be considered in the diagnostic work-up of affected individuals to improve diagnosis and potentially offer personalized treatment as increasing brain concentrations of NMDAR co-agonists appears to be a promising precision treatment approach successfully targeting deficient glutamatergic signaling in individuals with mental disorders, i.e. due to GRIN2Anull.
