Refine
Has Fulltext
- yes (331)
Is part of the Bibliography
- yes (331)
Year of publication
Document Type
- Journal article (331) (remove)
Keywords
- chronic kidney disease (17)
- heart failure (15)
- Fabry disease (13)
- adrenocortical carcinoma (13)
- mortality (12)
- inflammation (11)
- echocardiography (10)
- myocardial infarction (10)
- hemodialysis (9)
- prognosis (8)
- biomarker (7)
- cardiomyopathy (7)
- cortisol (6)
- depression (6)
- heart (6)
- obesity (6)
- therapy (6)
- CXCR4 (5)
- PET (5)
- anxiety (5)
- atherosclerosis (5)
- biomarkers (5)
- blood pressure (5)
- cardiovascular disease (5)
- cardiovascular diseases (5)
- enzyme replacement therapy (5)
- metabolomics (5)
- mouse (5)
- paraganglioma (5)
- pheochromocytoma (5)
- prevalence (5)
- type 2 diabetes (5)
- Cushing’s syndrome (4)
- cardiovascular events (4)
- coronary heart disease (4)
- cytokines (4)
- diabetes mellitus (4)
- diagnosis (4)
- epidemiology (4)
- fibrosis (4)
- hypercortisolism (4)
- hypertension (4)
- ischemic stroke (4)
- miRNA (4)
- mice (4)
- oxidative stress (4)
- radial (4)
- risk factors (4)
- survival (4)
- theranostics (4)
- ACTH (3)
- CMR (3)
- COVID-19 (3)
- FGFR (3)
- Heart failure (3)
- MRI (3)
- SOAT1 (3)
- adrenocortical cancer (3)
- amyloidosis (3)
- blood (3)
- cancer (3)
- cardiac hypertrophy (3)
- cardiac magnetic resonance imaging (3)
- cognitive decline (3)
- cognitive impairment (3)
- coronary artery disease (3)
- desmin (3)
- diabetes (3)
- dialysis (3)
- diet (3)
- end-stage renal disease (3)
- endoradiotherapy (3)
- follow-up (3)
- genetics (3)
- guidelines (3)
- hypertrophic cardiomyopathy (3)
- immune response (3)
- immunohistochemistry (3)
- impact (3)
- kidney (3)
- left ventricular hypertrophy (3)
- liraglutide (3)
- lymphocytes (3)
- machine learning (3)
- management (3)
- medicine (3)
- melanoma (3)
- mitotane (3)
- multicenter (3)
- osteoporosis (3)
- outcomes (3)
- quality of life (3)
- safety (3)
- treatment (3)
- vitamin D (3)
- 18F-FDG (2)
- 4D flow (2)
- C-X-C motif chemokine receptor 4 (2)
- CYP2W1 (2)
- Chronic kidney disease (2)
- Cushing’s disease (2)
- Depression (2)
- Diabetes mellitus (2)
- Enzyme replacement therapy (2)
- FGF-pathway (2)
- Fabry genotype (2)
- Fabry nephropathy (2)
- Fabry phenotype (2)
- GFAP (2)
- Germany (2)
- KDIGO (2)
- Kidney function (2)
- Medicine (2)
- Medizin (2)
- Mortality (2)
- NAFLD (2)
- Neurons (2)
- PPGL (2)
- Positronen-Emissions-Tomografie (2)
- Prevalence (2)
- Quality of life (2)
- Roux-en-Y gastric bypass surgery (2)
- SF-36 (2)
- TAVI (2)
- United States (2)
- WSS (2)
- [68Ga]PentixaFor (2)
- ablation (2)
- acute heart failure (2)
- acute kidney injury (2)
- adenomas (2)
- adrenal (2)
- adrenal cancer (2)
- adrenal crisis (2)
- adrenal insufficiency (2)
- adrenal tumours (2)
- adrenocortical tumors (2)
- age (2)
- aging (2)
- aldosterone (2)
- aneurysm (2)
- antimicrobial resistance (2)
- aortic arch (2)
- arrhythmia (2)
- association (2)
- blood flow (2)
- body mass index (2)
- body weight (2)
- bone (2)
- calcification (2)
- cancer treatment (2)
- carbohydrates (2)
- carcinomas (2)
- cardiac (2)
- cardiac MRI (2)
- cardiac surgery (2)
- cardiology (2)
- cardiovascular genetics (2)
- cardiovascular magnetic resonance (2)
- cardiovascular morbidity (2)
- cardiovascular risk factors (2)
- catecholamines (2)
- chemokine receptor (2)
- chronic cerebrovascular disease (2)
- chronic heart failure (2)
- chronic kidney-disease (2)
- convection volume (2)
- copeptin (2)
- deep learning (2)
- deformation (2)
- dementia (2)
- desmosomes (2)
- dialysis adequacy (2)
- efficacy (2)
- ejection fraction (2)
- gastric bypass (2)
- genome-wide association (2)
- glomerular filtration rate (2)
- glycemic control (2)
- guideline adherence (2)
- hemodiafiltration (2)
- hydrocortisone (2)
- hyperexpression techniques (2)
- identification (2)
- immune cells (2)
- immunotherapy (2)
- insulin resistance (2)
- internal medicine (2)
- kidneys (2)
- left ventricular ejection fraction (2)
- left ventricular mass (2)
- lysosomal storage disease (2)
- magnetic resonance imaging (2)
- mapping (2)
- medullary thyroid carcinoma (2)
- metaanalysis (2)
- mineral metabolism (2)
- morbidity (2)
- mouse models (2)
- multiple myeloma (2)
- myocardial work (2)
- natriuretic peptide (2)
- neuroendocrine tumor (2)
- neurofilament light chain (2)
- pediatric adrenocortical cancer (2)
- pediatric adrenocortical tumor (2)
- pembrolizumab (2)
- peptide tyrosine tyrosine (PYY) (2)
- placebo-controlled trial (2)
- population (2)
- positron emission tomography (2)
- postmenopausal women (2)
- precision medicine (2)
- primary prevention (2)
- prognostic factors (2)
- proteinuria (2)
- pulse wave velocity (2)
- quantification (2)
- radiotherapy (RT) (2)
- randomized controlled trial (2)
- receptor (2)
- recurrence (2)
- regulatory T cells (2)
- renal function (2)
- replacement (2)
- restrictive cardiomyopathy (2)
- sepsis (2)
- sizing (2)
- small interfering RNAs (2)
- stage renal-disease (2)
- stem cell transplantation (2)
- stroke (2)
- sudden cardiac death (2)
- surgery (2)
- therapeutic drug monitoring (2)
- troponin (2)
- tyrosine kinase inhibitor (2)
- uremic toxins (2)
- urine (2)
- validation (2)
- vandetanib (2)
- wall shear stress (2)
- 2- deoxy-2-(18F)fluoro-D-glucose (1)
- 2-deoxy-2-(18F)fluoro-D-glucose (1)
- 2-dimensional speckle tracking (1)
- 3 T (1)
- 4D flow MRI (1)
- 7 T (1)
- 7T (1)
- <sup>18</sup>F-FDG (1)
- <sup>68</sup>Ga-Pentixafor (1)
- A-delta fibers (1)
- ACC (1)
- ACC/AHA classification (1)
- ACM (1)
- AKI (1)
- ALT (1)
- ARDS (acute respiratory distress syndrome) (1)
- ARVC (1)
- ASE formula (1)
- ATP generation (1)
- ATRX (1)
- Addison's disease (1)
- Addisons disease (1)
- Adrenocortial carcinomas (1)
- African-americans (1)
- Agalsidase beta (1)
- Akutes Nierenversagen (1)
- Alpha-Galactosidase (1)
- Alpha-galactosidase (1)
- Alzheimer’s dementia (1)
- Amino acids (1)
- Anderson-Fabry Disease (1)
- Angst (1)
- Antigen 4 (1)
- Aorta (1)
- Aortic arch (1)
- Aplastic anemia (1)
- Apoptosis (1)
- Artificial Nuclear Pores (1)
- Atherosclerosis (1)
- Autoimmune-Diseases (1)
- B (1)
- B cells (1)
- BET Inhibitor (1)
- BIRC7 (1)
- BRAF mutation (1)
- BRAF(V600E) mutation (1)
- BRD4 (1)
- Biochemical-Diagnosis (1)
- Bioluminescence (1)
- Brain atrophy (1)
- Brownian ratchet (1)
- CASP (1)
- CCR7 (1)
- CD4+ T-cells (1)
- CD9 (1)
- CIED malfunction; pacemaker (PM) (1)
- CKD (1)
- CML (1)
- COH29 (1)
- COMT (1)
- COPD diagnosis (1)
- COVID‐19 vaccination (1)
- CRH stimulation test (1)
- CTNNB1 (1)
- CXCR7 (1)
- CYP2B6 (1)
- Ca cycling (1)
- Ca2+i handling (1)
- Calcineurin-NFATsignaling (1)
- Calcium Citrate (1)
- Calibration (1)
- Cancer genetics (1)
- Cardiac magnetic resonance imaging (1)
- Cardiac resynchronization therapy defibrillator (1)
- CardioMEMS™ HF-System (1)
- Cardiomyopathy (1)
- Cardiovascular diseases (1)
- Cardiovascular hospitalizations (1)
- Cardiovascular risk factors (1)
- Cardiovascular risk prediction (1)
- Carotid intima-media thickness (CIMT) (1)
- Carotid segment (1)
- Carotid ultrasound (1)
- Catheter Lock Solution (1)
- Catheter-related Bloodstream Infections (CRBSI) (1)
- Cell (1)
- Cell lung canger (1)
- Chronic Kidney-disease (1)
- Chronic heart failure (1)
- Chronic heart-failure (1)
- Chronic kidney-disease (1)
- Clinical prediction rule (1)
- Clinical proteomics (1)
- Clinical trial (1)
- Clinical-trials (1)
- Cognitive decline (1)
- Cohort study (1)
- Comorbidities (1)
- Contrast-enhanced CT (1)
- Copeptin (1)
- Coronavirus Disease 2019 (1)
- Cranial sutures (1)
- Cumulative incidence function (1)
- Cushing (1)
- Cushing syndrome (1)
- Cushing's (1)
- Cushing's disease (1)
- Cushings syndrome (1)
- Cytoskeleton (1)
- D313Y genotype (1)
- DIA-MS (1)
- DNA damage (1)
- DOTATOC (1)
- DSC2 (1)
- DSG2 (1)
- Dendritic Cells (1)
- Depression treatment (1)
- Depressive symptomatology (1)
- Desmoplakin (1)
- Diabetic nephropathies (1)
- Diabetic-nephropathy (1)
- Diagnosis (1)
- Diastocic Dysfunction (1)
- Dipeptidyl-peptidase IV inhibitors (1)
- Discovery (1)
- Disease prevalence (1)
- Diversity (1)
- Dokumentationsqualität (1)
- E/e’ (1)
- ECG (1)
- EMT (1)
- EP Procedures (1)
- ESC (1)
- EUROASPIRE (1)
- EUROASPIRE survey (1)
- Embryos (1)
- Enhancer elements (1)
- Epidemiology (1)
- Eplerenone (1)
- European Society (1)
- Expression (1)
- Extracellular volume (1)
- Extracorporeal membrane oxygenation (1)
- F-18-FDG PET/CT (1)
- FGF21 (1)
- FGFR-inhibitors (1)
- Fabry (1)
- Fabry Disease (FD) (1)
- Fabry cardiomyopathy (1)
- Fabry patient (1)
- Fabry-associated pain (1)
- False positive reactions (1)
- Family Investigation of Nephropathy and Diabetes (1)
- Female patients (1)
- Fibroblast Growth Factor-21 (1)
- Fontan’s Operation (1)
- FoxP3 Expression (1)
- Foxp3 (1)
- Framingham (1)
- G protein coupled receptors (1)
- GH response (1)
- GLA protein UCMGP (1)
- GLP-1 (1)
- GMPcGMP-dependent protein kinase I (1)
- GOLD (1)
- GRAPPA (1)
- Galactosidase-A gene (1)
- Gb3 and lyso-Gb3 biomarkers (1)
- General-population (1)
- Genome-wide association studies (1)
- Glial fibrillary acidic protein (1)
- Globotriaosylceramide (1)
- Glomerular-filtration-rate (1)
- Glycaemic control (1)
- Graves disease (1)
- HEK cells (1)
- HFpEF (1)
- HIV (1)
- HIV diagnosis and management (1)
- HLA (1)
- HUVEC (1)
- Haemodialysis (1)
- Hazards (1)
- Healthcare research (1)
- Heart failure with preserved ejection fraction (1)
- Heart failure with reduced ejection fraction (1)
- Hematopoietic cell transplant (1)
- Hemodialysis-patients (1)
- Hemoglobin A1C (1)
- HiGHmed (1)
- Hindbrain (1)
- Home monitoring (1)
- Homoarginine (1)
- Hypercortisolism (1)
- Hyperkalemia (1)
- Hyperosmotic Stress (1)
- ICD-coding of CKD (1)
- IDH1/2 (1)
- IGF-I (1)
- IMAZA (1)
- IP3 (1)
- Immune-System (1)
- Immunological Self-Tolerance (1)
- Immunosuppression (1)
- Impella (1)
- Infection control (1)
- Insulin therapy (1)
- Intensivtransport (1)
- Interhospitaltransfer (1)
- Interleukin-6 (1)
- Internet of Things devices (1)
- JQ1 (1)
- Juvenile biventricular cardiomyopathy (1)
- KWIC (1)
- Kaposi sarcoma (1)
- Klotho-related molecules (1)
- L-arginine (1)
- LCNEC (1)
- LDL cholesterol (1)
- LMNA (1)
- LND (1)
- LNE (1)
- LV dilatation (1)
- LV mass (1)
- LVNC (1)
- Lag time (1)
- Langzeitbeatmung (1)
- Linagliptin (1)
- Long COVID (1)
- Lyso-Gb3 (1)
- MASS (1)
- MEN1 (1)
- MOLLI (1)
- MR (1)
- MR guidance (1)
- MTL30 (1)
- MUST-Score (1)
- Magnetic resonance imaging (1)
- Mass-spectrometry (1)
- Measurement (1)
- Medullärer Schilddrüsenkrebs (1)
- Memory dysfunction (1)
- Men (1)
- Metanephrine (1)
- Methicillin-resistant staphylococcus aureus (1)
- Methodological quality (1)
- Mfn2 KO mice (1)
- Model (1)
- Molecular Channel Transport (1)
- Molekül (1)
- Morbidity (1)
- Morbus Fabry (1)
- Mouse (1)
- Mouse models (1)
- Multiparameter predictor (1)
- Multiple-Sclerosis (1)
- Myeloma (1)
- Myocardial infarction (1)
- Myocardial-Infarction (1)
- NASH (1)
- NCI-H295R (1)
- NEC (1)
- NET (1)
- NMR (1)
- NOP10 (1)
- NR3C1 (1)
- NSG animals (1)
- Natural-history data (1)
- Neprilysin inhibition (1)
- Network (1)
- New mexico (1)
- NfL (1)
- Non‐ischaemic cardiogenic shock (1)
- Normetanephrine (1)
- Nrf2 (1)
- OAT1 (1)
- OAT3 (1)
- OK cells (1)
- OSI (1)
- OXPHOS (1)
- Observational study (1)
- Onset hypertrophic cardiomyopathy (1)
- Oral antidiabetic drugs (1)
- Outcome survey (1)
- Outcomes (1)
- P-cresyl sulfate (1)
- PD-L1 (1)
- PF-05231023 (1)
- PHQ-9 (1)
- PRO (1)
- PTA (1)
- PWV (1)
- PYY3-36 (1)
- Pain (1)
- Pain-related evoked potentials (1)
- Palmoplantar keratoderma (1)
- Paraganglioma (1)
- Physical impairment (1)
- Plasma (1)
- Positron-emission-tomography (1)
- Postmarketing Experience (1)
- Predictive value of tests (1)
- Predictors (1)
- Preserved Ejection Fraction (1)
- Primary care (1)
- Probabilities (1)
- Prognostic impact (1)
- Progression (1)
- Protein (1)
- Psychopharmakologie (1)
- Psychotherapie (1)
- RAKI (1)
- RNA Expression (1)
- RNAScope (1)
- RNR (1)
- ROS (1)
- RRM2 (1)
- RYGB (1)
- Racial differences (1)
- Raman micro-spectroscopy (1)
- Recognition of depression (1)
- Regression (1)
- Remote device monitoring (1)
- Research design (1)
- Resistance (1)
- Risk (1)
- Risk-factors (1)
- Rotary EXcitation (REX) (1)
- Roux-en-Y Gastric Bypass (1)
- Roux-en-Y gastric bypass (1)
- SARS‐CoV‐2 infection (1)
- SASHA (1)
- SCORE (1)
- SGLT2 inhibitor (1)
- SGLT2 inhibitors (1)
- SNP (1)
- SR Ca leak (1)
- SR/mitochondria metabolic feedback (1)
- SSTR (1)
- ST-elevation myocardial infarction (1)
- STEMI (1)
- SUMO2 (1)
- Sample-sizes (1)
- Sars-CoV-2 (1)
- Self-navigation (1)
- Septal bulge (1)
- Severe Acute Respiratory Syndrome Coronavirus 2 (1)
- Sex-Hormones (1)
- ShMOLLI (1)
- Skull (1)
- Small fiber neuropathy (1)
- Society (1)
- Somites (1)
- Spin echo (1)
- Stage renal-disease (1)
- Stiffness (1)
- Subdistribution (1)
- Sudden cardiac death (1)
- Suppressive Function (1)
- Survival (1)
- Systemic-Lupus-Erythematosus (1)
- Systole (1)
- T cells (1)
- T-cells (1)
- T1 mapping (1)
- T1rho (1)
- T1ρ (1)
- TERT (1)
- TKI (1)
- TNF-alpha (1)
- TT\(_{1rho}\) mapping (1)
- T\(_{1P}\) dispersion (1)
- T\(_{1P}\) mapping (1)
- Tanzania (1)
- Taurolidine (1)
- Teichholz formula (1)
- Test accuracy (1)
- Tests (1)
- Thermodynamics (1)
- Thermodynamik (1)
- Time measurement (1)
- Transport (1)
- Treatment outcome (1)
- Tregs (regulatory T cells) (1)
- USP28 (1)
- USP8 (1)
- Utility (1)
- VAS (1)
- VEMP (1)
- Valvular heart-desease (1)
- Variants (1)
- Ventricular septal rupture (1)
- Weaning (1)
- X-chromosomal inactivation (1)
- XA (1)
- Young-patients (1)
- ZDF rats (1)
- Zebrafish (1)
- Zucker fatty fa/fa rats (1)
- [11C]-Choline PET/CT (1)
- [11C]-Methionine (1)
- [177Lu]/[90Y]PentixaTher (1)
- [177Lu]PentixaTher (1)
- [18F]FDG-PET-CT (1)
- [90Y]PentixaTher (1)
- [99mTc]-Sestamibi scan (1)
- [\(^{68}\)Ga] pentixafor (1)
- \(^{18}\)F-FDG (1)
- \(^{18}\)F-fluorodeoxyglucose (1)
- abdominal lymph node metastases (1)
- absorption (1)
- accelerated atherosclerosis (1)
- activated-receptor gamma (1)
- activation (1)
- acute respiratory distress syndrome (1)
- adaptive immune response (1)
- add-on (1)
- adenovirus (1)
- adenoviruses (1)
- adenylyl cyclase signaling cascade (1)
- adjuvant platinum-based chemotherapy (1)
- adjuvant therapy (1)
- adjuvant treatment (1)
- adrenal cortex hormones (1)
- adrenal cortex neoplasms (1)
- adrenal glands (1)
- adrenal imaging (1)
- adrenal surgery (1)
- adrenal tumor (1)
- adrenal tumors (1)
- adrenalectomia (1)
- adrenocortical (1)
- adrenocortical adenocarcinoma (1)
- adrenocortical adenoma (1)
- adrenocortical carcinoma (ACC) (1)
- adrenocortical cell line (1)
- adrenocortical development (1)
- adrenocortical tissues (1)
- adrenocortical tumor (1)
- adult patients (1)
- adverse effects (1)
- afatinib (1)
- agalsidase-beta (1)
- agnoists (1)
- albumin excretion rate (1)
- albuminuria (1)
- alcohol (1)
- alkaline phosphatase (1)
- allocation (1)
- allogeneic hematopoietic stem cell transplantation (1)
- alpha galactosidase (1)
- alpha-galactosidase-A (1)
- alpha/delta agonist GFT505 (1)
- amphiphilic block copolymer (1)
- anaemia (1)
- anatomy (1)
- anemia (1)
- animal model (1)
- animal models of human disease (1)
- antagonist (1)
- anti-drug antibodies (1)
- anti-myocardial (1)
- antibiotic prescription (1)
- antibodies (1)
- anticoagulation (1)
- antidiabetic agents (1)
- antimicrobial stewardship (1)
- antiphospholipid syndrome (1)
- antiretroviral therapy (1)
- antiretrovirals (1)
- anti‐SARS‐CoV‐2‐spike IgG (1)
- aorta (1)
- aortic valve (1)
- aortic valve disease (1)
- aortic valve disease percutaneous intervention (AVDP) (1)
- aortic valve stenosis (1)
- aortic valve stenosis (AS) (1)
- apolipoprotein E (1)
- apolipoprotein-E (1)
- apoptosis (1)
- arial fibrillation (1)
- arrhythmogenic cardiomyopathy (1)
- arterial elasticity (1)
- arterial stiffening (1)
- astrocytoma (1)
- at-home sampling (1)
- atheriosclerosis (1)
- atherogenic dyslipidaemia (1)
- atherosclerosis risk (1)
- atrial fibrillation (1)
- atypical (1)
- autoantibodies (1)
- autoantibody (1)
- autonomous cortisol secretion (1)
- avascular necrosis (1)
- awareness (1)
- balance (1)
- bardoxolone methyl (1)
- battery depletion (1)
- behavior (1)
- biocompatibility (1)
- bioinformatic clustering (1)
- biomarker prediction (1)
- biopsy (1)
- biopsy findings (1)
- blood coagulation factor XIII (1)
- blood plasma (1)
- blood pressure monitoring (1)
- blood-glucose control (1)
- blood–brain barrier (1)
- bone formation (1)
- bone metabolism (1)
- bone mineral density (1)
- brain natriuretic peptide (1)
- brain pathology (1)
- branched-chain amino acids (1)
- bull’s eye plot (1)
- buparlisib (1)
- c-MYC (1)
- calcineurin signaling cascade (1)
- calcium (1)
- calcium imaging (1)
- canagliflozin (1)
- cancer detection (1)
- cancer diagnosis (1)
- cancer risk (1)
- cancer risk factors (1)
- cancer types (1)
- cancer-testis antigens (1)
- candidate genes (1)
- carcinogenesis (1)
- carcinoma (1)
- carcinoma metastases to pancreas (1)
- cardiac amyloidosis (1)
- cardiac arrest (1)
- cardiac dysfunction (1)
- cardiac energy metabolism (1)
- cardiac function (1)
- cardiac implantable electronic devices (CIED) (1)
- cardiac implants (1)
- cardiac magnetic resonance (1)
- cardiac pacing (1)
- cardiac resynchronization therapy (CRT) (1)
- cardiac thrombi (1)
- cardiac training group (1)
- cardiac transplantation (1)
- cardiac ventricles (1)
- cardiogenetics (1)
- cardiomyopathies (1)
- cardiopulmonary bypass (1)
- cardiovascular MRI (1)
- cardiovascular care (1)
- cardiovascular death (1)
- cardiovascular drugs (1)
- cardiovascular magnetic-resonance (1)
- cardiovascular mortality (1)
- cardiovascular munster procam (1)
- cardiovascular outcomes (1)
- cardiovascularm disease (1)
- carotid artery disease (1)
- case report (1)
- caspase-3 (1)
- catenin (1)
- catheter tip (1)
- cell biology (1)
- cell cultures (1)
- cell fusion (1)
- cell staining (1)
- cells (1)
- cellular physiology (1)
- central nervous system (1)
- cerebrovascular diseases (1)
- channel transport (1)
- checkpoint inhibitors (1)
- child (1)
- cholesterol (1)
- cholesterol metabolism (1)
- chromosomes (1)
- chronic distress (1)
- chronic heart failure (CHF) (1)
- chronic kidney disease (CKD) (1)
- chronic myeloid leukemia (1)
- chronic thromboembolic pulmonary hypertension (1)
- chronotype (1)
- cigarette smoking (1)
- circadian rhythms (1)
- circadian therapy (1)
- circulating microRNA (1)
- classification (1)
- clearance (1)
- clinical (1)
- clinical data warehouse (1)
- clinical genetics (1)
- clinical manifestations (1)
- clinical routine data (1)
- clinical study (1)
- clinical systems (1)
- clinical trial (1)
- clonal hematopoiesis of indeterminate potential (1)
- cloning of putative human promoter sequence (1)
- closure AV fistula/AVM (CLAV) (1)
- coa reductase inhibitors (1)
- coagulation (1)
- coaptation line (1)
- coherent anti-Stokes Raman scattering (CARS) microscopy (1)
- colestilan (1)
- colloids (1)
- color-coded (1)
- combination (1)
- comorbidity (1)
- comparability (1)
- comparative genomic hybridization (1)
- complex (1)
- complex‐valued machine learning (1)
- complication (1)
- comprehensive psychosomatic assessment (1)
- computed tomography (1)
- confounders (1)
- congenital adrenal hyperplasia (1)
- consensus conference (1)
- contact force (1)
- contractility (1)
- converting enzyme-inhibition (1)
- cornea verticillata (1)
- coronary calcification (1)
- coronary-artery calcification (1)
- coronary-heart-disease (1)
- correction (1)
- cortical OAT1 (1)
- cortisol-producing adenoma (1)
- costs (1)
- creatine synthesis (1)
- creatinine (1)
- cryptogenic stroke (1)
- cyclic (1)
- cyclic nucleotides such as cyclic adenosine monophosphate (1)
- cytochrome P450 3A4 (CYP3A4) (1)
- cytoplasmic staining (1)
- cytosol (1)
- dabrafenib (1)
- data augmentation (1)
- data warehouse (1)
- death rates (1)
- deep-vein thrombosis (1)
- deficient mice (1)
- demography (1)
- desmin-related myopathy (1)
- desminopathy (1)
- desmocollin-2 (1)
- desmoglein-2 (1)
- deubiquitinases (1)
- dexamethasone suppression test (1)
- diabetes complications (1)
- diabetes insipidus (1)
- diabetes mellitus type 2 (1)
- diabetic cardiomyopathy (1)
- diabetic kidney disease (1)
- diabetic mouse (1)
- diabetic nephropathy (1)
- diagnosis in Fabry disease (1)
- diagnostic medicine (1)
- dialysate (1)
- dialyzer membrane (1)
- diastolic dysfunction (1)
- diastolic function (1)
- dietary approaches to stop hypertension (1)
- dietary sodium restriction (1)
- digital Health (1)
- digital phenotyping (1)
- digital subtraction angiography (1)
- dilated cardiomyopathy (1)
- dilated cardiomyopathy with ataxia (1)
- dimensions (1)
- disease (1)
- disease score (1)
- disease severity (1)
- dissection (1)
- distant metastases (1)
- dobutamine stress echocardiography (1)
- documentation quality (1)
- dogs (1)
- double knockout mice (1)
- double-blind (1)
- doule blind (1)
- down regulation (1)
- drug interaction (1)
- drug intoxication (1)
- drug monitoring (1)
- drug therapy (1)
- drug toxicity (1)
- drug transporter (1)
- drug treatment (1)
- drug–drug interactions (DDIs) (1)
- dynamic (1)
- dysfunction (1)
- early prognosis (1)
- early-stage osteonecrosis (1)
- ecological momentary assessment (1)
- ectopic (1)
- eculizumab (1)
- electronic data capture (1)
- electronic health records (1)
- electrophysiology (1)
- electroporation (1)
- empagliflozin (1)
- end stage renal disease (1)
- end-stage kidney disease (1)
- endocrine cancer (1)
- endocrinology (1)
- endogenous hypercortisolism (1)
- endothelial (1)
- endothelial cell interactions (1)
- endothelin-1 (1)
- endovascular (1)
- energy homeostasis (1)
- enoxaparin (1)
- entresto (1)
- entropy production (1)
- environmental health (1)
- environmental impact (1)
- eosinophils (1)
- epithelial markers (1)
- erythropoietin (1)
- euroaspire (1)
- evidence-based practice (1)
- expression (1)
- extended matching questions (1)
- extracellular matrix (1)
- extracellular matrix remodeling (1)
- fabry disease (1)
- factor XI (1)
- factor XII (1)
- failure (1)
- fall (1)
- fatal cardiovascular disease (1)
- fatty acids (1)
- fatty liver (1)
- feature selection (1)
- female Fabry patients (1)
- ferritin (1)
- fetuin A (1)
- fibroblast growth factor-23 (1)
- filamin-C (1)
- flow (1)
- flow dynamics (1)
- flow patterns (1)
- fluorescence resonance energy transfer (1)
- focal semental glomerulosclerosis (1)
- focused surgical approach (1)
- food consumption (1)
- fourth (1)
- fractionation membranev (1)
- fracture (1)
- fragmin (1)
- free energy (1)
- free light chains (1)
- functional magnetic resonance imaging (1)
- functional regurgitation (1)
- gastric cancer (1)
- gefitinib (1)
- gene (1)
- gene expression (1)
- gene variant (1)
- gene-environment interaction (1)
- gene-therapy (1)
- genetic analysis (1)
- genetic loci (1)
- genetic renal disease (1)
- genetically modified animals (1)
- genome-wide association study (1)
- genotype/phenotype correlation (1)
- genotyping (1)
- giant cell arteritis (1)
- glial damage (1)
- glial fibrillary acidic protein (1)
- glioblastoma (1)
- global outcomes (1)
- glomerular-filtration-rate (1)
- glomerulonephritis (1)
- glucocorticoid excess (1)
- glucocorticoid replacement (1)
- glucocorticoid replacement regimens (1)
- glucocorticoid replacement therapy (1)
- glucose homeostasis (1)
- glucose tolerance test (1)
- graft (1)
- graft versus host disease (1)
- green fluorescent protein (1)
- growth differentiation factor 15 (1)
- growth hormone deficiency (1)
- guideline implementation (1)
- guideline-directed medical therapy (1)
- gut microbiome (1)
- haemodiafiltration (1)
- haemodialysis (1)
- haplotype (1)
- hashimotos-thyroiditis (1)
- healing and remodelling processes (1)
- health care (1)
- health care research (1)
- health economics (1)
- health policy (1)
- health questionnaire (1)
- health risk assessment (1)
- healthcare workers (1)
- hearing loss (1)
- heart disease (1)
- heart failure training group (1)
- heart failure with mid-range ejection fraction (1)
- heart failure with reduced ejection fraction (1)
- heart rate (1)
- heme oxygenase-1 (1)
- hemoglobin (1)
- heodialysis patients (1)
- high denisty lipoprotein (1)
- high dose dexamethasone suppression test (1)
- high-dose atorvastatin (1)
- high-resolution analysis (1)
- hip fracture (1)
- histopathology (1)
- home telemonitoring (1)
- homeostasis (1)
- homeostasisIon channels (1)
- hormones (1)
- hospitalization (1)
- human behaviour (1)
- human serum albumin (1)
- hydroxy-dabrafenib (1)
- hypercholesterolemia (1)
- hyperosmolality (1)
- hyperparathyroidism (1)
- hyperphosphataemia (1)
- hypersensitivity (1)
- hyponatremia (1)
- hypopituitary patients (1)
- hypothalamic gene expression (1)
- iPSC-CMs (1)
- identical twins (1)
- idiopathic osteonecrosis (1)
- imaging (1)
- imaging TTE/TEE (ITTE) (1)
- immune check inhibitor (1)
- immune checkpoint inhibitor (ICI) (1)
- immune-related adverse events (1)
- immunity (1)
- immuno-modulation (1)
- immunoassays (1)
- immunofluorescence (1)
- immunohistochemistry techniques (1)
- immunosenescence (1)
- immunotherapy-induced hypophysitis (1)
- implantable cardioverter defibrillator (ICD) (1)
- implantation (1)
- in silico analysis (1)
- in vivo (1)
- inappropriate prescription (1)
- incidence (1)
- incremental cost-effectiveness ratio (ICER) (1)
- indoxyl sulfate (1)
- induced insulin-release (1)
- inebilizumab (1)
- infarction size (1)
- infection (1)
- infections (1)
- inflammaging (1)
- information extraction (1)
- inherited metabolic disorders (1)
- inos (1)
- insufficiency (1)
- insulin tolerance test (1)
- intake (1)
- intensive care medicine (1)
- intensive care transport (1)
- intensive glucose control (1)
- interhospital transfer (1)
- interleukin-6 (1)
- interleukin-8 (1)
- intermediate filaments (1)
- interparticle interaction (1)
- intragastric balloon (1)
- ionic strength (1)
- ipilimumab (1)
- iron (1)
- ischemia (1)
- ischemia-reperfusion injury (1)
- ischemic (1)
- ischemic acute kidney injury model (1)
- isoproterenol (1)
- isturisa (1)
- italian population (1)
- kidney disease (1)
- kidney disease; (1)
- kidney ischemia/reperfusion injury (1)
- kidney-disease CKD (1)
- kinase (1)
- kinase inhibitors (1)
- kinases (1)
- lactase persistence (1)
- lactic acidosis (1)
- lactose (1)
- large animal models (1)
- late gadolinium enhancement (1)
- laxative (1)
- leaflet (1)
- left lateral wall (1)
- left ventricular geometric abnormality (1)
- left ventricular geometry (1)
- left ventricular mass index (1)
- left ventricular performance (1)
- left ventricular remodeling (1)
- left ventricular thrombusv (1)
- left-ventricular hypertrophy (1)
- leptin system (1)
- lesion formation (1)
- lesion size (1)
- lesions (1)
- leukocyte adhesion (1)
- leukocytes (1)
- lifestyle (1)
- linkage (1)
- lipid droplets (1)
- lipid-lowering therapy (1)
- lipoprotein apheresis (1)
- lipoprotein(a) (1)
- lipoxygenase (1)
- liquid chromatography tandem mass spectrometry (LC-MS/MS (1)
- liquid chromatography–tandem mass spectrometry (LC–MS/MS) (1)
- livin (1)
- lncRNA (1)
- long-term ventilation (1)
- longitudinal studies (1)
- loss (1)
- low molecular weight (1)
- low-gradient AS (1)
- lower limit of normal (1)
- lung cancer (1)
- lymph node dissection (1)
- lymph nodes (1)
- lymphadenectomy (1)
- lysosomal storage disorder (1)
- lyso‐Gb3 (1)
- m exercise training (1)
- mHealth (1)
- macrovascular (1)
- magnetic resonance (1)
- magnetic resonance spectroscopy (1)
- magnetic resonsance imaging (1)
- malignant tumors (1)
- malnutrition (1)
- marrow (1)
- mass spectrometry (1)
- mass spectronomy (1)
- meat (1)
- medical data integration center (1)
- medical dialysis (1)
- medical informatics initiative (1)
- medical students (1)
- medical therapy (1)
- medication extraction (1)
- medium cut-off dialyzer (1)
- medullary thyroid cancer (1)
- men born (1)
- menopause (1)
- mental impairment (1)
- mesenchymal markers (1)
- meta-analysis (1)
- metabolically unhealthy obesity (1)
- metabolism (1)
- metachronous (1)
- metastasis (1)
- metastatic (1)
- metformin (1)
- metyrapone (1)
- miR-182-5p (1)
- miR-183 cluster (1)
- miR-483-5p (1)
- mices (1)
- microscopy (1)
- microvascular (1)
- mild (1)
- mineral bone density (1)
- mineralocorticoid antagonist (1)
- minerals (1)
- mitochondria (1)
- mitochondria function and morphology (1)
- mitochondrial mRyR1 (1)
- mitofusin 2 (1)
- mitral valve (1)
- mobile crowdsensing (1)
- mobile health (1)
- model (1)
- modified-release hydrocortisone (1)
- molecular biology (1)
- molecular diagnostics (1)
- molecular medicine (1)
- monocytes (1)
- motion detector (1)
- multi-tyrosine kinase inhibitor (1)
- multidetector computed-tomography (1)
- multiple choice questions (1)
- multiple sclerosis (1)
- multivariate data analysis (1)
- mutation (1)
- mutation databases (1)
- mutation triggers (1)
- mutations (1)
- myocardial aging (1)
- myocardial lipid content (1)
- myocardial work efficiency (1)
- myocardial fibrosis (1)
- myocardial-infarction (1)
- myocardium (1)
- natural history (1)
- natural-history data (1)
- nerve fibers (1)
- neural networks (1)
- neuroblastoma – diagnosis (1)
- neurofibromatosis type 1 (1)
- neuroinflammation (1)
- neurological (1)
- neurological complications (1)
- neurology (1)
- neuromyelitis optica spectrum disorders (1)
- neurons (1)
- neuropathy (1)
- neuroscience (1)
- neutral loss (1)
- neutrophils (1)
- nictric-oxide (1)
- nitric oxide (1)
- nitric oxide synthase (1)
- nivolumab (1)
- non-equilibrium thermodynamics (1)
- non-triggered (1)
- noncontact monitoring (1)
- nontraumatic osteonecrosis of the femoral head (1)
- normal adrenal glands (1)
- normal values (1)
- notch signaling (1)
- nuclear staining (1)
- nutritional counseling (1)
- nutritional medical needs (1)
- nutritional risk screening (1)
- obesity surgery (1)
- observational study (1)
- occupational-status (1)
- oligonucleotides (1)
- on-site examination (1)
- oncology (1)
- oncology outpatients (1)
- openEHR (1)
- operation (1)
- opossum kidney cells (1)
- oral glucose (1)
- organoid (1)
- oscillating biomagnetic fields (1)
- osilodrostat (1)
- osimertinib (1)
- osmotic stimulation (1)
- osteocalcin (1)
- outcome (1)
- overload (1)
- p-cresyl sulfate (1)
- paired (1)
- pandemia (1)
- panel (1)
- papillary (1)
- papillary thyroid carcinoma (PTC) (1)
- parallel imaging (1)
- parathyroid adenoma (1)
- parathyroid carcinoma (1)
- parathyroid hormone (1)
- paravalvular regurgitation (1)
- pathogenesis (1)
- pathophysiology (1)
- patient survival (1)
- patients’ awareness (1)
- pediatric (1)
- pediatric adrenocortical adenoma (1)
- pediatric adrenocortical carcinoma (1)
- peptide tyrosine tyrosine 3-36 (PYY3-36) (1)
- peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) (1)
- percutaneous valve therapy (PVT) (1)
- perioperative chemotherapy (1)
- peritoneal carcinomatosis (1)
- personalised medicine (1)
- personalized antimicrobial therapy (1)
- personalized medicine (1)
- personalized treatment (1)
- pharmacoepidemiology (1)
- pharmacokinetics (1)
- pharmacotherapy (1)
- phase IV (1)
- phase-contrast CMR (1)
- phase-contrast MRI (1)
- pheochromocytoma/paraganglioma (1)
- phosphate homeostasis (1)
- phosphatidylcholines (1)
- phospholipid fatty acids (1)
- phosphorylated tau protein (1)
- phosphorylation (1)
- physical activity (1)
- physicians’ awareness (1)
- physiologically based pharmacokinetic (PBPK) modeling (1)
- pig (1)
- pioglitazone (1)
- piperacillin/tazobactam (1)
- pituitary (1)
- pituitary adenomas (1)
- pituitary gland (1)
- placebo (1)
- plant-derived metabolites (1)
- plaque (1)
- plaque characteristics (1)
- plasma (1)
- plasma NMR (1)
- plasma proteins (1)
- plasmid construction (1)
- platelet adhesion (1)
- platelets (1)
- pleural mesothelioma (1)
- podocyte (1)
- polarization (1)
- poly(2-oxazoline) (1)
- polyglandular autoimmune syndrome (1)
- polymorphism (1)
- polymyalgia rheumatica (1)
- population pharmacokinetics (1)
- population-based (1)
- population-based study (1)
- posaconazole (1)
- post-traumatic stress disorder (1)
- postoperativ (1)
- posttraumatische Belastungsstörung (1)
- poultry (1)
- preanalytical conditions (1)
- preclinical research (1)
- prediction model (1)
- predictive marker (1)
- premature mortality (1)
- preserved ejection fraction (1)
- preventive medicine (1)
- primary aldosteronism (1)
- primary healthcare (1)
- primary hyperparathyroidism (1)
- primary hypophysitis (1)
- primary polydipsia (1)
- prognostic biomarker (1)
- prognostic marker (1)
- prognostic markers (1)
- progression (1)
- propionic acid (1)
- prospective (1)
- prostaglandin e2 (1)
- prostate cancer (1)
- protein binding (1)
- protein expression (1)
- protein-bound solutes (1)
- protein-bound uremic toxins (1)
- proteomic (1)
- pseudo-severe AS (1)
- psychiatric disorders (1)
- psychopharmacology (1)
- psychotherapy (1)
- public health (1)
- pulmonary artery pressure (1)
- pulmonary cancer (1)
- pulse-wave velocity (1)
- quantitative MRI (1)
- radical resection (1)
- radii (1)
- radiofrequency ablation (1)
- radioiodine (1)
- radioiodine therapy (1)
- radiotherapy (1)
- randomized controlled-trial (1)
- randomized trial (1)
- rare diseases (1)
- rat kidney (1)
- ravulizumab (1)
- real-world (1)
- rearranged during transfection (1)
- recombination hotspot (1)
- recommendations (1)
- recovery (1)
- recurrence free survival (1)
- recurrence survival (1)
- recurrence-free survival (1)
- recurrent Tako-Tsubo cardiomyopathy (1)
- reference data (1)
- refugee healthcare (1)
- regression analysis (1)
- regulation of expression (1)
- regurgitation (1)
- remote monitoring (1)
- removal (1)
- renal artery (1)
- renal disease (1)
- renal dysfunction (1)
- renal fibrosis (1)
- renal osteodystrophy (1)
- renal replacement therapy (1)
- renal system (1)
- renoprotection (1)
- repeated (1)
- repeated surgery (1)
- reperfusion (1)
- replacement therapy (1)
- reporter gen assay (1)
- reproductive disorders (1)
- research infrastructure (1)
- residual cardiovascular risk (1)
- respiratory signs and symptoms (1)
- retrospective (1)
- review (1)
- re‐transplantation (1)
- rheumatoid arthritis (1)
- right ventricular dysfunction (1)
- risk (1)
- risk factor control (1)
- risk prediction scores (1)
- rodent model (1)
- root (1)
- ruxolitinib (1)
- rygb (1)
- sacubitril-valsartan (1)
- sarcoidosis (1)
- satralizumab (1)
- scale (1)
- sclerostin (1)
- secondary data usage (1)
- secondary prevention (1)
- segmentation (1)
- self-gating (1)
- self-navigation (1)
- selpercatinib (1)
- semantic interoperability (1)
- septal hypertrophy (1)
- sequence databases (1)
- seroprevalence (1)
- serotonin (1)
- serotonin transporter deficient mice (1)
- serum (1)
- serum creatinine (1)
- sevelamer (1)
- severe renal insufficiency (1)
- sex addiction (1)
- sex differences (1)
- shear stress (1)
- shimming (1)
- short Synacthen test (1)
- short term (1)
- short-chain fatty acids (1)
- signal voids (1)
- signs (1)
- signs and symptoms (1)
- single nucleotide polymorphisms (1)
- skin diseases (1)
- sleeve gastrectomy (1)
- small animal (1)
- smoking (1)
- sodium (1)
- sodium-glucose co-transporter-2 inhibitors (1)
- solubility enhancement (1)
- somatic mutations (1)
- somatostatin receptor (1)
- speckle tracking imaging (1)
- speech recognition (1)
- sphingolipids (1)
- spin lock (1)
- spin-lock (1)
- spironolactone (1)
- sports and exercise medicine (1)
- standard heparin (1)
- standardization (1)
- state space (1)
- statement (1)
- statins (1)
- statistical mechanics (1)
- stenosis (1)
- steroid measurement (1)
- stress instructions (1)
- subjective health-status (1)
- sudden death (1)
- sulfonylurea (1)
- super-obesity (1)
- surgical and invasive medical procedures (1)
- surgical oncology (1)
- surgical repair (1)
- surgical treatment (1)
- surveillance (1)
- susceptibility (1)
- symptoms (1)
- systemic micro-inflammation oxidative stress (1)
- systems biology (1)
- t-lymphocytes (1)
- target therapies (1)
- targeted gene panel (1)
- targeted metabolomics (1)
- targeted therapy (1)
- targeted treatment (1)
- task force (1)
- telemedicine (1)
- telomeres (1)
- temperature (1)
- tenting (1)
- term fenofibrate therapy (1)
- therapeutic approach (1)
- therapeutic management (1)
- therapeutic options (1)
- thermodynamics (1)
- third (1)
- three-dimensional echocardiography (1)
- thromboinflammation (1)
- thrombopoiesis (1)
- thyroid carcinoma (TC) (1)
- tight junctions (1)
- timing (1)
- tissue (1)
- tocilizumab (1)
- tomography (1)
- trametinib (1)
- transcatheter valveimplantation (TVI) (1)
- transfection (1)
- transfer learning (1)
- transgenic rats (1)
- translation (1)
- translational research (1)
- transport experiments (1)
- treatment outcome (1)
- trial design (1)
- tricuspid pressure gradient (1)
- triglyceride-rich lipoproteins (1)
- troponin T (1)
- tumor (1)
- tumor microenvironment (1)
- tumor-infiltrating (1)
- tumors (1)
- type 2 (1)
- type-1 diabetes mellitus (1)
- type-2 diabetes mellitus (1)
- tyrosine kinase inhibitor (TKI) (1)
- tyrosine kinase inhibitors (1)
- ublituximab (1)
- ultrahigh field (1)
- ultrahigh-field (1)
- ultrahigh-field MRI (1)
- unfractionated heparin (1)
- univentricular heart (1)
- unsupervised clustering (1)
- uremic toxin (1)
- urinary protein excretion (1)
- usability (1)
- use (1)
- user-centered design (1)
- validity (1)
- variant (1)
- vascular calcification (1)
- vascular surgery (1)
- vemurafenib (1)
- ventricular tachycardia (1)
- vertigo (1)
- viral infection (1)
- vitamins (1)
- volume (1)
- volumetric absorptive micro-sampling (VAMS) (1)
- weaning (1)
- whole exome sequencing (1)
- wires (1)
- yellow fluorescent protein (1)
- zebrafish (1)
- α-galactosidase A (1)
- α‐GalA 3D‐structure (1)
Institute
- Medizinische Klinik und Poliklinik I (331) (remove)
Sonstige beteiligte Institutionen
- Zentraleinheit Klinische Massenspektrometrie (4)
- Apotheke, Universitätsklinikum Würzburg (1)
- Center for Interdisciplinary Clinical Research, Würzburg University, Würzburg, Germany (1)
- Datenintegrationszentrum Würzburg (DIZ) (1)
- Interdisziplinäre Biomaterial- und Datenbank Würzburg (ibdw) (1)
- Interdisziplinäres Amyloidosezentrum Nordbayern (1)
- Johns Hopkins School of Medicine (1)
- Johns Hopkins University School of Medicine (1)
- Klinische Studienzentrale (Universitätsklinikum) (1)
- Krankenhaushygiene und Antimicrobial Stewardship, Universitätsklinikum Würzburg (1)
Background
CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.
Methods
Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.
Results
Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.
Conclusions
In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.
A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.
Differences between immunotherapy-induced and primary hypophysitis—a multicenter retrospective study
(2022)
Objective
Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH)
Design
Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH.
Methods
All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected.
Results
Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002).
Conclusions
Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.
Purpose
Pheochromocytomas and Paragangliomas (PPGL) result in chronic catecholamine excess and serious health complications. A recent study obtained a metabolic signature in plasma from PPGL patients; however, its targeted nature may have generated an incomplete picture and a broader approach could provide additional insights. We aimed to characterize the plasma metabolome of PPGL patients before and after surgery, using an untargeted approach, and to broaden the scope of the investigated metabolic impact of these tumors.
Design
A cohort of 36 PPGL patients was investigated. Blood plasma samples were collected before and after surgical tumor removal, in association with clinical and tumor characteristics.
Methods
Plasma samples were analyzed using untargeted nuclear magnetic resonance (NMR) spectroscopy metabolomics. The data were evaluated using a combination of uni- and multi-variate statistical methods.
Results
Before surgery, patients with a nonadrenergic tumor could be distinguished from those with an adrenergic tumor based on their metabolic profiles. Tyrosine levels were significantly higher in patients with high compared to those with low BMI. Comparing subgroups of pre-operative samples with their post-operative counterparts, we found a metabolic signature that included ketone bodies, glucose, organic acids, methanol, dimethyl sulfone and amino acids. Three signals with unclear identities were found to be affected.
Conclusions
Our study suggests that the pathways of glucose and ketone body homeostasis are affected in PPGL patients. BMI-related metabolite levels were also found to be altered, potentially linking muscle atrophy to PPGL. At baseline, patient metabolomes could be discriminated based on their catecholamine phenotype.
Introduction
Medium-cut-off (MCO) dialyzers may beneficially impact outcomes in patients on hemodialysis.
Methods
In a randomized, controlled trial in maintenance hemodialysis patients, the new Nipro ELISIO-17HX MCO dialyzer was compared to the Baxter Theranova 400 filter regarding middle molecule removal. Furthermore, the suitability of two assays for free lambda-light chain (λFLC) detection (Freelite vs. N-Latex) was verified.
Results
ELISIO-HX achieved slightly lower reduction ratios for β2-microglobulin (71.8 ± 6.0 vs. 75.3 ± 5.8%; p = 0.001), myoglobin (54.7 ± 8.6 vs. 64.9 ± 8.7%; p < 0.001), and kappa-FLC (62.1 ± 8.8 vs. 56.3 ± 7.7%; p = 0.021). λFLC reduction ratios were more conclusive with the Freelite assay and not different between ELISIO-HX and Theranova (28.4 ± 3.9 vs. 38.7 ± 13.4%; p = 0.069). The albumin loss of Theranova was considerably higher (2.14 ± 0.45 vs. 0.77 ± 0.25 g; p = 0.001) and the Global Removal ScoreLoss alb largely inferior (30.6 ± 7.4 vs. 82.4 ± 29.2%/g; p = 0.006) to ELISIO-HX.
Conclusions
The new ELISIO-HX expands the choice of dialyzers for MCO hemodialysis.
To evaluate an iterative learning approach for enhanced performance of robust artificial‐neural‐networks for k‐space interpolation (RAKI), when only a limited amount of training data (auto‐calibration signals [ACS]) are available for accelerated standard 2D imaging.
Methods
In a first step, the RAKI model was tailored for the case of limited training data amount. In the iterative learning approach (termed iterative RAKI [iRAKI]), the tailored RAKI model is initially trained using original and augmented ACS obtained from a linear parallel imaging reconstruction. Subsequently, the RAKI convolution filters are refined iteratively using original and augmented ACS extracted from the previous RAKI reconstruction. Evaluation was carried out on 200 retrospectively undersampled in vivo datasets from the fastMRI neuro database with different contrast settings.
Results
For limited training data (18 and 22 ACS lines for R = 4 and R = 5, respectively), iRAKI outperforms standard RAKI by reducing residual artifacts and yields better noise suppression when compared to standard parallel imaging, underlined by quantitative reconstruction quality metrics. Additionally, iRAKI shows better performance than both GRAPPA and standard RAKI in case of pre‐scan calibration with varying contrast between training‐ and undersampled data.
Conclusion
RAKI benefits from the iterative learning approach, which preserves the noise suppression feature, but requires less original training data for the accurate reconstruction of standard 2D images thereby improving net acceleration.
Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans, translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled Würzburg Adipositas Study (WAS) and from RYGB-treated rats (n = 6) as well as body-weight-matched controls (n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI −34.3% (OP) vs. −1.2% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss.
(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m\(^2\) (36–74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ\(^2\) (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ\(^2\) (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease.
Usability of a mHealth solution using speech recognition for point-of-care diagnostic management
(2023)
The administrative burden for physicians in the hospital can affect the quality of patient care. The Service Center Medical Informatics (SMI) of the University Hospital Würzburg developed and implemented the smartphone-based mobile application (MA) ukw.mobile1 that uses speech recognition for the point-of-care ordering of radiological examinations. The aim of this study was to examine the usability of the MA workflow for the point-of-care ordering of radiological examinations. All physicians at the Department of Trauma and Plastic Surgery at the University Hospital Würzburg, Germany, were asked to participate in a survey including the short version of the User Experience Questionnaire (UEQ-S) and the Unified Theory of Acceptance and Use of Technology (UTAUT). For the analysis of the different domains of user experience (overall attractiveness, pragmatic quality and hedonic quality), we used a two-sided dependent sample t-test. For the determinants of the acceptance model, we employed regression analysis. Twenty-one of 30 physicians (mean age 34 ± 8 years, 62% male) completed the questionnaire. Compared to the conventional desktop application (DA) workflow, the new MA workflow showed superior overall attractiveness (mean difference 2.15 ± 1.33), pragmatic quality (mean difference 1.90 ± 1.16), and hedonic quality (mean difference 2.41 ± 1.62; all p < .001). The user acceptance measured by the UTAUT (mean 4.49 ± 0.41; min. 1, max. 5) was also high. Performance expectancy (beta = 0.57, p = .02) and effort expectancy (beta = 0.36, p = .04) were identified as predictors of acceptance, the full predictive model explained 65.4% of its variance. Point-of-care mHealth solutions using innovative technology such as speech-recognition seem to address the users’ needs and to offer higher usability in comparison to conventional technology. Implementation of user-centered mHealth innovations might therefore help to facilitate physicians’ daily work.
Background
The importance of chronic kidney disease (CKD) and anaemia has not been comprehensively studied in asymptomatic patients at risk for heart failure (HF) versus those with symptomatic HF. We analysed the prevalence, characteristics and prognostic impact of both conditions across American College of Cardiology/American Heart Association (ACC/AHA) precursor and HF stages A–D.
Methods and results
2496 participants from three non-pharmacological German Competence Network HF studies were categorized by ACC/AHA stage; stage C patients were subdivided into C1 and C2 (corresponding to NYHA classes I/II and III, respectively). Overall, patient distribution was 8.1%/35.3%/32.9% and 23.7% in ACC/AHA stages A/B/C1 and C2/D, respectively. These subgroups were stratified by the absence ( – ) or presence ( +) of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) and anaemia (haemoglobin in women/men < 12/ < 13 g/dL). The primary outcome was all-cause mortality at 5-year follow-up. Prevalence increased across stages A/B/C1 and C2/D (CKD: 22.3%/23.6%/31.6%/54.7%; anaemia: 3.0%/7.9%/21.7%/33.2%, respectively), with concordant decreases in median eGFR and haemoglobin (all p < 0.001). Across all stages, hazard ratios [95% confidence intervals] for all-cause mortality were 2.1 [1.8–2.6] for CKD + , 1.7 [1.4–2.0] for anaemia, and 3.6 [2.9–4.6] for CKD + /anaemia + (all p < 0.001). Population attributable fractions (PAFs) for 5-year mortality related to CKD and/or anaemia were similar across stages A/B, C1 and C2/D (up to 33.4%, 30.8% and 34.7%, respectively).
Conclusions
Prevalence and severity of CKD and anaemia increased across ACC/AHA stages. Both conditions were individually and additively associated with increased 5-year mortality risk, with similar PAFs in asymptomatic patients and those with symptomatic HF.
We assume that a specific health constraint, e.g., a certain aspect of bodily function or quality of life that is measured by a variable X, is absent (or irrelevant) in a healthy reference population (Ref0), and it is materially present and precisely measured in a diseased reference population (Ref1). We further assume that some amount of this constraint of interest is suspected to be present in a population under study (SP). In order to quantify this issue, we propose the introduction of an intuitive measure, the population comparison index (PCI), that relates the mean value of X in population SP to the mean values of X in populations Ref0 and Ref1. This measure is defined as PCI[X] = (mean[X|SP] − mean[X|Ref0])/(mean[X|Ref1] − mean[X|Ref0]) × 100[%], where mean[X|.] is the average value of X in the respective group of individuals. For interpretation, PCI[X] ≈ 0 indicates that the values of X in the population SP are similar to those in population Ref0, and hence, the impairment measured by X is not materially present in the individuals in population SP. On the other hand, PCI[X] ≈ 100 means that the individuals in SP exhibit values of X comparable to those occurring in Ref1, i.e., the constraint of interest is equally present in populations SP and Ref1. A value of 0 < PCI[X] < 100 indicates that a certain percentage of the constraint is present in SP, and it is more than in Ref0 but less than in Ref1. A value of PCI[X] > 100 means that population SP is even more affected by the constraint than population Ref1.
Acute and chronic cardiac disorders predispose to alterations in cognitive performance, ranging from mild cognitive impairment to overt dementia. Although this association is well-established, the factors inducing and accelerating cognitive decline beyond ageing and the intricate causal pathways and multilateral interdependencies involved remain poorly understood. Dysregulated and persistent inflammatory processes have been implicated as potentially causal mediators of the adverse consequences on brain function in patients with cardiac disease. Recent advances in positron emission tomography disclosed an enhanced level of neuroinflammation of cortical and subcortical brain regions as an important correlate of altered cognition in these patients. In preclinical and clinical investigations, the thereby involved domains and cell types of the brain are gradually better characterized. Microglia, resident myeloid cells of the central nervous system, appear to be of particular importance, as they are extremely sensitive to even subtle pathological alterations affecting their complex interplay with neighboring astrocytes, oligodendrocytes, infiltrating myeloid cells, and lymphocytes. Here, we review the current evidence linking cognitive impairment and chronic neuroinflammation in patients with various selected cardiac disorders including the aspect of chronic neuroinflammation as a potentially druggable target.
Background
International guidelines emphasise the role of radiotherapy (RT) for the management of advanced adrenocortical carcinoma (ACC). However, the evidence for this recommendation is very low.
Methods
We retrospectively analysed all patients who received RT for advanced ACC in five European centres since 2000. Primary endpoint: time to progression of the treated lesion (tTTP). Secondary endpoints: best objective response, progression-free survival (PFS), overall survival (OS), adverse events, and the establishment of predictive factors by Cox analyses.
Results
In total, 132 tumoural lesions of 80 patients were treated with conventional RT (cRT) of 50–60 Gy (n = 20) or 20–49 Gy (n = 69), stereotactic body RT of 35–50 Gy (SBRT) (n = 36), or brachytherapy of 12–25 Gy (BT) (n = 7). Best objective lesional response was complete (n = 6), partial (n = 52), stable disease (n = 60), progressive disease (n = 14). Median tTTP was 7.6 months (1.0–148.6). In comparison to cRT\(_{20-49Gy}\), tTTP was significantly longer for cRT\(_{50-60Gy}\) (multivariate adjusted HR 0.10; 95% CI 0.03–0.33; p < 0.001) and SBRT (HR 0.31; 95% CI 0.12–0.80; p = 0.016), but not for BT (HR 0.66; 95% CI 0.22–1.99; p = 0.46). Toxicity was generally mild and moderate with three grade 3 events. No convincing predictive factors could be established.
Conclusions
This largest published study on RT in advanced ACC provides clear evidence that RT is effective in ACC.
Neurofibromatosis type 1 (NF1) is a genetic multisystemic autosomal dominant disorder determining reduced life expectancy due to higher risk of developing benign and malignant tumors. Low levels of vitamin D and reduced bone mineral density (BMD) have been reported in young patients with NF1. However, correlation between vitamin D and NF1 phenotype needs to be elucidated. Aim of this study was to assess vitamin D levels and bone metabolism in NF1 patients, analyzing potential correlations with clinical phenotype. A cross-sectional study was carried out in a monocentric series of NF1 patients, evaluating genotype, clinical phenotype, BMD, biochemical evaluation with focus on serum 25OH-vitamin D, parathyroid hormone (PTH), calcium and phosphate levels. Correlations between clinical manifestations, neurofibromas, and vitamin D status have been studied in comparison with healthy controls. 31 NF1 adult patients were matched for sex, age and body mass index with 31 healthy controls. A significantly difference in vitamin D level emerged in NF1 patients compared to controls. Interestingly low vitamin D levels correlated with a more aggressive phenotype and with a bigger size of neurofibromas. These data underline that vitamin D deficiency/insufficiency may play a role in clinical severity of neurofibromas in patients with NF1, suggesting the need to check bone status and replace vitamin D in these patients.
Background
Patients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012–13; and EA-V, 2016–17) in Germany.
Methods
The EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in Würzburg (EA-IV, EA-V), Halle (EA-V), and Tübingen (EA-V).
Results
384 EA-V participants (median age 69.0 years, 81.3% male) and 536 EA-IV participants (median age 68.7 years, 82.3% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8% vs. 19.6%) while the proportion of prediabetes was similarly high in the remaining population (62.1% vs. 61.0%).
Conclusion
Between 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.
Background: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers. Methods: Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed. Results: 39 patients (M:F = 26:13), with a median age of 64 years (44–83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4–169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46–12.07, p = 0.008 and HR = 13.56, 95%CI 2.45–74.89, p = 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23–38.83, p = 0.002 and HR = 11.88, 95%CI 2.28–61.84, p = 0.003, respectively). Conclusion: After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy.
Purpose: This study analyses a large number of cancer patients with CIEDs for device malfunction and premature battery depletion by device interrogation after each radiotherapy fraction and compares different guidelines in regard to patient safety. Methods: From 2007 to 2022, a cohort of 255 patients was analyzed for CIED malfunctions via immediate device interrogation after every RT fraction. Results: Out of 324 series of radiotherapy treatments, with a total number of 5742 CIED interrogations, nine device malfunctions (2.8%) occurred. Switching into back-up/safety mode and software errors occurred four times each. Once, automatic read-out could not be performed. The median prescribed cumulative dose at planning target volume (PTV) associated with CIED malfunction was 45.0 Gy (IQR 36.0–64.0 Gy), with a median dose per fraction of 2.31 Gy (IQR 2.0–3.0 Gy). The median maximum dose at the CIED at time of malfunction was 0.3 Gy (IQR 0.0–1.3 Gy). No correlation between CIED malfunction and maximum photon energy (p = 0.07), maximum dose at the CIED (p = 0.59) nor treatment localization (p = 0.41) could be detected. After excluding the nine malfunctions, premature battery depletion was only observed three times (1.2%). Depending on the national guidelines, 1–9 CIED malfunctions in this study would have been detected on the day of occurrence and in none of the cases would patient safety have been compromised. Conclusion: Radiation-induced malfunctions of CIEDs and premature battery depletion are rare. If recommendations of national safety guidelines are followed, only a portion of the malfunctions would be detected directly after occurrence. Nevertheless, patient safety would not be compromised.
Psychosocial factors affect mental health and health-related quality of life (HRQL) in a complex manner, yet gender differences in these interactions remain poorly understood. We investigated whether psychosocial factors such as social support and personal and work-related concerns impact mental health and HRQL differentially in women and men during the first year of the COVID-19 pandemic. Between June and October 2020, the first part of a COVID-19-specific program was conducted within the “Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB)” cohort study, a representative age- and gender-stratified sample of the general population of Würzburg, Germany. Using psychometric networks, we first established the complex relations between personal social support, personal and work-related concerns, and their interactions with anxiety, depression, and HRQL. Second, we tested for gender differences by comparing expected influence, edge weight differences, and stability of the networks. The network comparison revealed a significant difference in the overall network structure. The male (N = 1370) but not the female network (N = 1520) showed a positive link between work-related concern and anxiety. In both networks, anxiety was the most central variable. These findings provide further evidence that the complex interplay of psychosocial factors with mental health and HRQL decisively depends on gender. Our results are relevant for the development of gender-specific interventions to increase resilience in times of pandemic crisis.
Air pollution is associated with morbidity and mortality worldwide. We investigated the impact of improved air quality during the economic lockdown during the SARS-Cov2 pandemic on emergency room (ER) admissions in Germany. Weekly aggregated clinical data from 33 hospitals were collected in 2019 and 2020. Hourly concentrations of nitrogen and sulfur dioxide (NO2, SO2), carbon and nitrogen monoxide (CO, NO), ozone (O3) and particulate matter (PM10, PM2.5) measured by ground stations and meteorological data (ERA5) were selected from a 30 km radius around the corresponding ED. Mobility was assessed using aggregated cell phone data. A linear stepwise multiple regression model was used to predict ER admissions. The average weekly emergency numbers vary from 200 to over 1600 cases (total n = 2,216,217). The mean maximum decrease in caseload was 5 standard deviations. With the enforcement of the shutdown in March, the mobility index dropped by almost 40%. Of all air pollutants, NO2 has the strongest correlation with ER visits when averaged across all departments. Using a linear stepwise multiple regression model, 63% of the variation in ER visits is explained by the mobility index, but still 6% of the variation is explained by air quality and climate change.
Long-term sequelae in hospitalized Coronavirus Disease 2019 (COVID-19) patients may result in limited quality of life. The current study aimed to determine health-related quality of life (HRQoL) after COVID-19 hospitalization in non-intensive care unit (ICU) and ICU patients. This is a single-center study at the University Hospital of Wuerzburg, Germany. Patients eligible were hospitalized with COVID-19 between March 2020 and December 2020. Patients were interviewed 3 and 12 months after hospital discharge. Questionnaires included the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L), patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder 7 scale (GAD-7), FACIT fatigue scale, perceived stress scale (PSS-10) and posttraumatic symptom scale 10 (PTSS-10). 85 patients were included in the study. The EQ5D-5L-Index significantly differed between non-ICU (0.78 ± 0.33 and 0.84 ± 0.23) and ICU (0.71 ± 0.27; 0.74 ± 0.2) patients after 3- and 12-months. Of non-ICU 87% and 80% of ICU survivors lived at home without support after 12 months. One-third of ICU and half of the non-ICU patients returned to work. A higher percentage of ICU patients was limited in their activities of daily living compared to non-ICU patients. Depression and fatigue were present in one fifth of the ICU patients. Stress levels remained high with only 24% of non-ICU and 3% of ICU patients (p = 0.0186) having low perceived stress. Posttraumatic symptoms were present in 5% of non-ICU and 10% of ICU patients. HRQoL is limited in COVID-19 ICU patients 3- and 12-months post COVID-19 hospitalization, with significantly less improvement at 12-months compared to non-ICU patients. Mental disorders were common highlighting the complexity of post-COVID-19 symptoms as well as the necessity to educate patients and primary care providers about monitoring mental well-being post COVID-19.
Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research
(2023)
A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.
Background
Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking.
Methods
Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl.
Results
A total of 260 patients were enrolled (147 women (56.5%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0%) and PACS (21.9%) than in NFA (8.1%). Over time, 40/124 (32.3%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing’s syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9%; PACS, 24.0%; ACS, 39.0%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3% vs. 81.9% and 92.0%; p<0.05), diabetes (23.8% vs. 35.6% and 40.0%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95%-CI 0.89-13.29; ACS: HR 5.96, 95%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95%-CI 0.94-5.32; ACS: HR 2.60, 95%-CI 0.87-7.79; p=0.1). Twenty-five (12.6%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0% at diagnosis to 61.7% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group.
Conclusion
Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy).
Background
Guideline-directed medical therapy (GDMT) is the cornerstone in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) and novel substances such as sacubitril/valsartan (S/V) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) have demonstrated marked clinical benefits. We investigated their implementation into real-world HF care in Germany before, during, and after the COVID-19 pandemic period.
Methods
The IQVIA LRx data set is based on ∼80% of 73 million people covered by the German statutory health insurance. Prescriptions of S/V were used as a proxy for HFrEF. Time trends were analysed between Q1/2016 and Q2/2023 for prescriptions for S/V alone and in combination therapy with SGLT2i.
Findings
The number of patients treated with S/V increased from 5260 in Q1/2016 to 351,262 in Q2/2023. The share of patients with combination therapy grew from 0.6% (29 of 5260) to 14.2% (31,128 of 219,762) in Q2/2021, and then showed a steep surge up to 54.8% (192,429 of 351,262) in Q2/2023, coinciding with the release of the European Society of Cardiology (ESC) guidelines for HF in Q3/2021. Women and patients aged >80 years were treated less often with combined therapy than men and younger patients. With the start of the COVID-19 pandemic, the number of patients with new S/V prescriptions dropped by 17.5% within one quarter, i.e., from 26,855 in Q1/2020 to 22,145 in Q2/2020, and returned to pre-pandemic levels only in Q1/2021.
Interpretation
The COVID-19 pandemic was associated with a 12-month deceleration of S/V uptake in Germany. Following the release of the ESC HF guidelines, the combined prescription of S/V and SGLT2i was readily adopted. Further efforts are needed to fully implement GDMT and strengthen the resilience of healthcare systems during public health crises.
Objectives
The spectrum of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) represents highly inflammatory rheumatic diseases. Patients mostly report severe physical impairment. Possible consequences for mental health have been scarcely studied. The aim of this study was to investigate psychological well-being in the context of GCA and PMR.
Methods
Cross-sectional study with N = 100 patients with GCA and/or PMR (GCA-PMR). Patient-reported outcomes (PROs) were measured using the Short Form 36 Version 2 (SF-36v2) and visual analog scale (VAS) assessment. Moreover, the Patient Health Questionnaire 9 (PHQ-9) was used in 35 of 100 patients to detect depression. To compare PROs with physician assessment, VAS was also rated from physician perspective. To assess a possible association with inflammation itself, serological parameters of inflammation (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) were included.
Results
In all scales of the SF-36v2 except General Health (GH) and in the physical and mental sum score (PCS, MCS), a significant impairment compared to the German reference collective was evident (MCS: d = 0.533, p < 0.001). In the PHQ-9 categorization, 14 of the 35 (40%) showed evidence of major depression disorder. VAS Patient correlated significantly with PHQ-9 and SF-36 in all categories, while VAS Physician showed only correlations to physical categories and not in the mental dimensions. Regarding inflammatory parameters, linear regression showed CRP to be a complementary significant positive predictor of mental health subscale score, independent of pain.
Conclusion
PRO show a relevant impairment of mental health up to symptoms of major depression disorder. The degree of depressive symptoms is also distinctly associated with the serological inflammatory marker CRP.
Serum liquid chromatography–tandem mass spectrometry (LC–MS/MS) steroid profiling is used for the diagnosis of adrenocortical carcinoma (ACC). Guidelines recommend endocrine work-up in addition to radiological imaging for follow-up in ACC, but data on this topic are scarce. Patients were included in this retrospective study if pre-therapeutic hormone values, regular tumour evaluation by imaging, steroid measurements by LC–MS/MS, and details on therapies were available. The utility of steroid profiles in detecting recurrence or disease progression was assessed, whereby “endocrine progress” was defined by an elevation of at least 3 of 13 analysed hormones. Cohort A included 47 patients after R0 resection, of whom 15 experienced recurrence and 32 did not. In cohort B, 52 patients with advanced disease (including 7 patients of cohort A with recurrence) could be evaluated on 74 visits when progressive disease was documented. In 20 of 89 cases with documented disease progression, “endocrine progress” was detectable prior to radiological progress. In these cases, recurrence/progression was detected at a median of 32 days earlier by steroid measurement than by imaging, with 11-deoxycortisol and testosterone being the most sensitive markers. Notably, these patients had significantly larger tumour burden. In conclusion, steroid profiling by LC–MS/MS is of value in detecting recurrent/progressive disease in ACC.
Adrenocortical carcinoma (ACC) represents a rare tumor entity with limited treatment options and usually rapid tumor progression in case of metastatic disease. As further treatment options are needed and ACC metastases are sensitive to external beam radiation, novel theranostic approaches could complement established therapeutic concepts. Recent developments focus on targeting adrenal cortex-specific enzymes like the theranostic twin [\(^{123/131}\)I]IMAZA that shows a good image quality and a promising therapeutic effect in selected patients. But other established molecular targets in nuclear medicine such as the C-X-C motif chemokine receptor 4 (CXCR4) could possibly enhance the therapeutic regimen as well in a subgroup of patients. The aims of this review are to give an overview of innovative radiopharmaceuticals for the treatment of ACC and to present the different molecular targets, as well as to show future perspectives for further developments since a radiopharmaceutical with a broad application range is still warranted.
Background: Monitoring the vital signs of delirious patients in an intensive care unit (ICU) is challenging, as they might (un-)intentionally remove devices attached to their bodies. In mock-up scenarios, we systematically assessed whether a motion detector (MD) attached to the bed may help in identifying emergencies. Methods: We recruited 15 employees of the ICU and equipped an ICU bed with an MD (IRON Software GmbH, Grünwald, Germany). Participants were asked to replay 22 mock-up scenes of one-minute duration each: 12 scenes with movements and 10 without movements, of which 5 were emergency scenes (“lying dead-still, with no or very shallow breathing”). Blinded recordings were presented to an evaluation panel consisting of an experienced ICU nurse and a physician, who was asked to assess and rate the presence of motions. Results: Fifteen participants (nine women; 173 ± 7.0 cm; 78 ± 19 kg) joined the study. In total, 286 out of 330 scenes (86.7%) were rated correctly. Ratings were false negative (FN: “no movements detected, but recorded”) in 7 out of 180 motion scenes (3.9%). Ratings were false positive (FP: “movements detected, but not recorded”) in 37 out of 150 scenes (24.7%), more often in men than women (26 out of 60 vs. 11 out of 90, respectively; p < 0.001). Of note, in 16 of these 37 FP-rated scenes, a vibrating mobile phone was identified as a potential confounder. The emergency scenes were correctly rated in 64 of the 75 runs (85.3%); 10 of the 11 FP-rated scenes occurred in male subjects. Conclusions: The MD allowed for identifying motions of test subjects with high sensitivity (96%) and acceptable specificity (75%). Accuracy might increase further if activities are recorded continuously under real-world conditions.
Highlights
• Loss of DNAJC19's DnaJ domain disrupts cardiac mitochondrial structure, leading to abnormal cristae formation in iPSC-CMs.
• Impaired mitochondrial structures lead to an increased mitochondrial respiration, ROS and an elevated membrane potential.
• Mutant iPSC-CMs show sarcomere dysfunction and a trend to more arrhythmias, resembling DCMA-associated cardiomyopathy.
Background
Dilated cardiomyopathy with ataxia (DCMA) is an autosomal recessive disorder arising from truncating mutations in DNAJC19, which encodes an inner mitochondrial membrane protein. Clinical features include an early onset, often life-threatening, cardiomyopathy associated with other metabolic features. Here, we aim to understand the metabolic and pathophysiological mechanisms of mutant DNAJC19 for the development of cardiomyopathy.
Methods
We generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two affected siblings with DCMA and a gene-edited truncation variant (tv) of DNAJC19 which all lack the conserved DnaJ interaction domain. The mutant iPSC-CMs and their respective control cells were subjected to various analyses, including assessments of morphology, metabolic function, and physiological consequences such as Ca\(^{2+}\) kinetics, contractility, and arrhythmic potential. Validation of respiration analysis was done in a gene-edited HeLa cell line (DNAJC19tv\(_{HeLa}\)).
Results
Structural analyses revealed mitochondrial fragmentation and abnormal cristae formation associated with an overall reduced mitochondrial protein expression in mutant iPSC-CMs. Morphological alterations were associated with higher oxygen consumption rates (OCRs) in all three mutant iPSC-CMs, indicating higher electron transport chain activity to meet cellular ATP demands. Additionally, increased extracellular acidification rates suggested an increase in overall metabolic flux, while radioactive tracer uptake studies revealed decreased fatty acid uptake and utilization of glucose. Mutant iPSC-CMs also showed increased reactive oxygen species (ROS) and an elevated mitochondrial membrane potential. Increased mitochondrial respiration with pyruvate and malate as substrates was observed in mutant DNAJC19tv HeLa cells in addition to an upregulation of respiratory chain complexes, while cellular ATP-levels remain the same. Moreover, mitochondrial alterations were associated with increased beating frequencies, elevated diastolic Ca\(^{2+}\) concentrations, reduced sarcomere shortening and an increased beat-to-beat rate variability in mutant cell lines in response to β-adrenergic stimulation.
Conclusions
Loss of the DnaJ domain disturbs cardiac mitochondrial structure with abnormal cristae formation and leads to mitochondrial dysfunction, suggesting that DNAJC19 plays an essential role in mitochondrial morphogenesis and biogenesis. Moreover, increased mitochondrial respiration, altered substrate utilization, increased ROS production and abnormal Ca\(^{2+}\) kinetics provide insights into the pathogenesis of DCMA-related cardiomyopathy.
Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study
(2024)
Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.