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.
Abstract Introduction: In RRMM, increasing rates of pt attrition and decreasing durability of responses with each line of therapy (LOT) necessitate early treatment (tx) with the most effective therapies. Immunotherapies that are widely accessible across different MM tx settings have the potential to change the trajectory of RRMM. Teclistamab (Tec), the first approved BCMA×CD3 bispecific antibody (BsAb) for heavily pretreated RRMM, provided deep, durable responses in MajesTEC-1, with improved efficacy and safety in earlier LOTs. Daratumumab (Dara), a standard-of-care (SoC) foundational CD38 targeted therapy with direct on-tumor activity, has been shown to deplete immunosuppressive T-cells and expand cytotoxic T-cells, creating an immune-permissive microenvironment for synergistic Tec-mediated killing of MM cells. MajesTEC-3 (NCT05083169) evaluates Tec-Dara vs SoC DPd/DVd in RRMM. We report initial results for this first phase 3 study of BsAb therapy in MM. Methods: Eligible pts had 1-3 prior LOTs including a PI and lenalidomide (Len; pts with 1 prior LOT must have been Len-refractory) with progressive disease (PD) on or after the last LOT. Pts with prior BCMA-directed therapy or refractory to anti-CD38 were excluded; prior anti-CD38 exposure was permitted. Pts were randomized 1:1 to Tec-Dara or DPd/DVd. The Tec-Dara group received 28-day cycles (C) of Tec (1.5 mg/kg QW in C1-2 [C1 preceded by the approved step-up dose schedule]; 3 mg/kg Q2W in C3-6; and 3 mg/kg Q4W in C7+) with Dara; steroids were not required after C1 Day 8. Tec and Dara dosing were aligned with the approved Dara schedule. DPd/DVd were administered per approved schedules. Progression-free survival (PFS) by IRC was the primary endpoint; secondary endpoints included complete response or better (≥CR), overall response, minimal residual disease (MRD) negativity (10–5; next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety. Results: 587 pts were randomized (Tec-Dara, n=291; DPd/DVd, n=296). Median (range) age was 64 (25-88) yrs, median number of prior LOTs was 2 (1-3). With 34.5-mo median follow-up, Tec-Dara significantly improved PFS vs DPd/DVd (HR, 0.17; 95% CI, 0.12-0.23; P<0.0001); mPFS was NR and 18.1 mo, and 36-mo PFS rate was 83.4% and 29.7%, respectively. PFS benefit was consistent across all prespecified and clinically relevant pt subgroups, including age ≥75 yrs, Len-refractory, high-risk cytogenetics, ≥60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposed. Significantly higher rates of ≥CR (81.8% vs 32.1%; OR, 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs 75.3%; OR, 2.65; 95% CI, 1.68-4.18), and MRD-negativity (58.4% vs 17.1%; OR, 6.78; 95% CI, 4.53-10.15) were observed with Tec-Dara (P<0.0001). There were 45 deaths with Tec-Dara and 96 with DPd/DVd, primarily due to PD (4.6%; 20.3%). OS significantly favored Tec-Dara (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001), including across all prespecified subgroups. The 36-mo OS rates were 83.3% and 65.0%, respectively and >90% of Tec-Dara pts alive at 6 mo were also alive at 30 mo. Median time to worsening of MM symptoms was NR with Tec-Dara vs 39.9 mo with DPd/DVd (HR, 0.50; 95% CI, 0.34-0.72; P=0.0002). At data cutoff, 49.4% of pts remained on study tx (Tec-Dara, 71.0%; DPd/DVd, 28.3%). Median tx duration was twice as long with Tec-Dara vs DPd/DVd (32.4 vs 16.1 mo). Frequency of grade 3/4 (Tec-Dara, 95.1%; DPd/DVd, 96.6%) and grade 5 (7.8%; 6.2%) treatment-emergent adverse events (TEAEs), were comparable (safety set: Tec-Dara, n=283; DPd/DVd, n=290). Serious TEAEs occurred in 70.7% Tec-Dara and 62.4% DPd/DVd pts; tx discontinuations due to TEAEs were low (4.6% vs 5.5%). Any grade infections occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd pts, respectively; grade 3/4 infections occurred in 54.1% and 43.4%. New onset grade ≥3 infections decreased over time, coinciding with transition to Q4W dosing and supported by antimicrobial and Ig prophylaxis guidance. CRS rate was 60.1% (grade 1/2: 44.2%/15.9%) and ICANS was 1.1% with Tec-Dara. Conclusion: We demonstrate the clinically remarkable and statistically significant PFS and OS benefits of Tec-Dara vs SoC triplets in RRMM, with 83.4% of Tec-Dara pts alive and progression-free at 3 yrs. Infections with Tec-Dara were well managed with established protocols. This highly effective, off-the-shelf, immunotherapy combination represents a new SoC for RRMM as early as first relapse.
