Longitudinal trajectories in renal function before and after heart failure hospitalization among patients with heart failure with preserved ejection fraction in the PARAGON-HF trial.

Aims: Worsening renal function may impact long-term outcomes in heart failure (HF). However, little is known about the longitudinal trajectories in renal function in relation to HF hospitalization or how this high-risk clinical event impacts renal outcomes.

Methods And Results: In PARAGON-HF, we evaluated the association between recency of prior HF hospitalization (occurring pre-randomization) and subsequent first renal composite outcome: (i) time to ≥50% decline in estimated glomerular filtration rate (eGFR); (ii) development of end-stage renal disease; or (iii) death attributable to renal causes.

Organic Anion Transporter Gene Variants Associated With Plasma Exposure and Long-Term Response to Atrasentan in Patients With Diabetic Kidney Disease.

Plasma exposure of the endothelin receptor antagonist atrasentan varies between individuals and is associated with nephroprotective effects and the risk of heart failure. We examined the influence of genetic polymorphisms on atrasentan plasma exposure and pharmacodynamic effects. We performed a substudy of the Study of Diabetic Nephropathy With Atrasentan (SONAR) trial which enrolled adults with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate: 25-75 mL/min/1.

Facilitating EMA binding test performance using fluorescent beads combined with next-generation sequencing.

The eosin-5'-maleimide (EMA) binding test is widely used as diagnostic test for hereditary spherocytosis (HS), one of the most common haemolytic disorders in Caucasian populations. We recently described the advantages of replacing the use of healthy control blood samples with fluorescent beads in a modified EMA binding assay. In this study we further explore this novel approach.

Clinically important changes in right ventricular volume and function in pulmonary arterial hypertension assessed with cardiac magnetic resonance imaging.

Right ventricular (RV) dilatation predicts clinical worsening in pulmonary arterial hypertension (PAH) and RV volumes can be measured with high precision using cardiovascular magnetic resonance imaging. In regular follow-up of patients and in studies of improvement in RV function, knowledge of clinically significant changes of RV volumes and function are of relevance. Patients with PAH were followed with cardiovascular magnetic resonance imaging and clinical assessment at 6-month intervals.

Estimates of epilepsy prevalence, psychiatric co-morbidity and cost.

Purpose: This study estimated epilepsy prevalence, psychiatric co-morbidity and annual costs associated with epilepsy.

Methods: We used Danish national health registers to identify persons diagnosed with epilepsy and psychiatric disorders, and persons using antiseizure medication and persons using drugs for psychiatric disorders. We calculated the prevalence of epilepsy and co-morbid psychiatric disorders in Denmark on December 31, 2016, using information on epilepsy and psychiatric disorders based on combinations of hospital contacts and use of antiseizure and psychoactive medication.

Niraparib treatment for patients with -mutated ovarian cancer: review of clinical data and therapeutic context.

We reviewed clinical data for niraparib monotherapy in -mutated (m) epithelial ovarian cancer (OC), contextualizing results with data from other poly(ADP-ribose) polymerase inhibitors (PARPis). Niraparib reduced the likelihood of progression or death by 60% as first-line maintenance therapy and by 73-78% in recurrent disease. In heavily pretreated OC, efficacy was greater in the m versus non-m cohort.

Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities.

BACKGROUND: GLOW is a phase 3 trial evaluating the efficacy and safety of ibrutinib-venetoclax in older patients and/or those with comorbidities with previously untreated chronic lymphocytic leukemia (CLL). METHODS: We randomly assigned (1:1) patients 65 years of age or older or those 18 to 64 years of age who also had a Cumulative Illness Rating Scale (CIRS) score greater than 6 (CIRS scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or creatinine clearance of less than 70 ml/min, to ibrutinib-venetoclax (3 cycles ibrutinib lead-in, then 12 cycles ibrutinib-venetoclax) or chlorambucil-obinutuzumab (6 cycles). The primary end point was progression-free survival (PFS) assessed by an independent review committee.

Increase in BNP in Response to Endothelin-Receptor Antagonist Atrasentan Is Associated With Incident Heart Failure.

Background: The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization.

Objectives: The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk.

Methods: Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.

GMP Compliant Production of a Cryopreserved Adipose-Derived Stromal Cell Product for Feasible and Allogeneic Clinical Use.

The emerging field of advanced therapy medicinal products (ATMP) holds promise of treating a variety of diseases. Adipose-derived stromal cells (ASCs) are currently being marketed or tested as cell-based therapies in numerous clinical trials. To ensure safety and efficacy of treatments, high-quality products must be manufactured.

Anatomical validation of automatic respiratory motion correction for coronary 18F-sodium fluoride positron emission tomography by expert measurements from four-dimensional computed tomography.

Background: Respiratory motion correction is of importance in studies of coronary plaques employing F-NaF; however, the validation of motion correction techniques mainly relies on indirect measures such as test-retest repeatability assessments. In this study, we aim to compare and, thus, validate the respiratory motion vector fields obtained from the positron emission tomography (PET) images directly to the respiratory motion observed during four-dimensional cine-computed tomography (CT) by an expert observer.

Purpose: To investigate the accuracy of the motion correction employed in a software (FusionQuant) used for evaluation of F-NaF PET studies by comparing the respiratory motion of the coronary plaques observed in PET to the respiratory motion observed in 4D cine-CT images.

Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials.

Background: Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes.

Methods: We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF.

Setting a Benchmark for Quality of Care: Update on Best Practices in Transcatheter Aortic Valve Replacement Programs.

Transcatheter aortic valve replacement (TAVR) is an established therapy for the treatment of severe aortic stenosis. The evolution of technology and procedural approaches has facilitated the development of streamlined clinical pathways to optimize patient care and improve outcomes. The revision of historical practices and the adoption of contemporary best practices throughout patients' journey from referral to discharge create opportunities to drive quality improvement.

Robotic liver resection in Denmark: Report of the first 50 cases at Rigshospitalet Copenhagen.

While most centers around the globe still consider open hepatic resection as the standard, innovative centers step in light of future developments of the robotic platform forward and introduce a robotic liver program while skipping the laparoscopic approach for its technological flaws. This applies also for our Department of Surgery and Transplantation at Rigshospitalet, Copenhagen University Hospital in Denmark. We herewith present as-to our best knowledge-the first center in Scandinavia our experience with the initial 50 robotic liver resections.

Clinical Outcomes Related to Background Diuretic Use and New Diuretic Initiation in Patients With HFrEF.

Background: Up to 20% of patients in heart failure with reduced ejection fraction (HFrEF) trials are not taking diuretic agents at baseline, but little is known about them.

Objectives: The aim of this study was to examine outcomes in patients with HFrEF not taking diuretic medications and after diuretic medications are started.

Methods: Patient characteristics and outcomes were compared between patients taking or not taking diuretic drugs at baseline in the ATMOSPHERE (Aliskiren Trial of Minimizing Outcomes for Patients With Heart Failure) and PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) trials combined.

NetSurfP-3.0: accurate and fast prediction of protein structural features by protein language models and deep learning.

Recent advances in machine learning and natural language processing have made it possible to profoundly advance our ability to accurately predict protein structures and their functions. While such improvements are significantly impacting the fields of biology and biotechnology at large, such methods have the downside of high demands in terms of computing power and runtime, hampering their applicability to large datasets. Here, we present NetSurfP-3.

Five-Year Outcomes After Coronary Computed Tomography Angiography (From 110,599 Patients in a Danish Nationwide Register-Based Follow-Up Study).

The long-term cardiovascular risk for patients examined with coronary computed tomography angiography (CCTA) to rule out coronary heart disease compared with population controls remains unexplored. A nationwide register-based study including first-time CCTA-examined patients between 2007 and 2017 in Denmark alive 180 days post-CCTA was conducted. We evaluated 5-year outcomes of myocardial infarction (MI) or revascularization and all-cause mortality in 3 distinct CCTA-groups: (1) no post-CCTA preventive pharmacotherapy use (cholesterol-lowering drugs, antiplatelets, or anticoagulants); (2) post-CCTA preventive pharmacotherapy use; and (3) revascularization or MI within 180 days post-CCTA.

Pancreatic surgery during the COVID-19 pandemic 2020-2021: an observational cohort study from a third level referral center.

Background: During the COVID pandemic there has been limited access to elective surgery including oncologic surgery in several countries world-wide. The aim of this study was to investigate if there was any lockdown effect on pancreatic surgery with special focus on malignant pancreatic and periampullary tumours.

Methods: Patients who underwent pancreatic surgery during the two Danish lockdown periods from 11.

Social determinants of tuberculosis: a nationwide case-control study, Denmark, 1990-2018.

Background: The global vision is a world free of tuberculosis (TB). Even in resource-rich TB low-incidence settings, we need more focus on the role of social risk factors to end the TB epidemic.

Methods: Nationwide, retrospective register-based, case-control study from 1990 to 2018, including all TB patients in Denmark ≥18 years old (n = 9581) matched 1:3 on sex and age with population controls.

Adaptive Immune Response to Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity.

Background: We aimed to characterise the adaptive immune response to complex (MABSC) and its cross-reactivity with complex (MAC) and (Bacille Calmette-Guérin, BCG) in cystic fibrosis (CF) patients and non-CF controls in terms of lymphocyte proliferation and immunophenotyping, cytokine production and anti-MABSC IgG plasma levels.

Methods: In this cross-sectional analysis, peripheral blood mononuclear cells (PBMC) from CF patients with MABSC (CF/MABSC, n=12), MAC infection history (CF/MAC, n=5), no NTM history (CF/NTM-, n=15), BCG-vaccinated (C/BCG+, n=9) and non-vaccinated controls (C/BCG-, n=8) were cultured for four days under stimulation with an in-house MABSC lysate and we used flow cytometry to assess lymphocyte proliferation (given by lymphoblast formation) and immunophenotypes. Cytokine production was assessed after overnight whole blood stimulation with the same lysate, and anti-MABSC IgG levels were measured in plasma from non-stimulated blood.

DeepLoc 2.0: multi-label subcellular localization prediction using protein language models.

The prediction of protein subcellular localization is of great relevance for proteomics research. Here, we propose an update to the popular tool DeepLoc with multi-localization prediction and improvements in both performance and interpretability. For training and validation, we curate eukaryotic and human multi-location protein datasets with stringent homology partitioning and enriched with sorting signal information compiled from the literature.

Cardiac remodelling - Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology.

In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes.

Clinical evaluation versus magnetic resonance imaging findings in patients with radicular arm pain-A pragmatic study.

Objectives: Cervical nerve root compression can lead to radiculopathy in the arm. Some studies have reported low accuracy in determining the responsible nerve root in both cervical and lumbar regions. This prospective, observational, pragmatic study aimed to determine the accuracy of the clinical evaluation relative to magnetic resonance imaging (MRI) findings in patients with arm radiculopathy.