Refine
Has Fulltext
- yes (351)
Is part of the Bibliography
- yes (351)
Year of publication
Document Type
- Journal article (195)
- Doctoral Thesis (155)
- Book article / Book chapter (1)
Keywords
- COVID-19 (15)
- Blut-Hirn-Schranke (13)
- blood-brain barrier (12)
- ARDS (11)
- inflammation (11)
- Maligne Hyperthermie (9)
- Myokardprotektion (9)
- Schmerz (9)
- endothelial cells (8)
- malignant hyperthermia (8)
- molecular docking (8)
- Schlaganfall (7)
- blood–brain barrier (7)
- cytokines (7)
- pain (7)
- stroke (7)
- Anästhesie (6)
- Desfluran (6)
- Entzündung (6)
- Erbrechen (6)
- Herzinfarkt (6)
- PONV (6)
- Präkonditionierung (6)
- SARS-CoV-2 (6)
- Schmerzforschung (6)
- preconditioning (6)
- sepsis (6)
- volatile anesthetics (6)
- CRPS (5)
- Medizin (5)
- Schmerztherapie (5)
- Tight junction (5)
- critical illness (5)
- in vitro (5)
- microRNA (5)
- tight junctions (5)
- Ischämische Präkonditionierung (4)
- Neuropathischer Schmerz (4)
- Polytrauma (4)
- Sevofluran (4)
- acute kidney injury (4)
- acute respiratory distress syndrome (4)
- blood brain barrier (4)
- breast cancer (4)
- cardioprotection (4)
- chronic pain (4)
- critical care (4)
- desflurane (4)
- expression (4)
- halothane (4)
- microdialysis (4)
- neuropathic pain (4)
- sevoflurane (4)
- traumatic brain injury (4)
- Amisulprid (3)
- Anästhetikum (3)
- Chronischer Schmerz (3)
- First Responder (3)
- Gibbs free energy of binding (3)
- HFOV (3)
- Halothan (3)
- Intensivtransport (3)
- Kardioprotektion (3)
- Komplexes regionales Schmerzsyndrom (3)
- Meerschweinchen (3)
- Mikrodialyse (3)
- Narkose (3)
- Nausea (3)
- Neuralgie (3)
- Notfallmedizin (3)
- Propofol (3)
- Regionalanästhesie (3)
- Schädel-Hirn-Trauma (3)
- Succinylcholine (3)
- Systematische Übersichtsarbeit (3)
- Therapie (3)
- Tiermodell (3)
- Ultraschall (3)
- Ventilation (3)
- Videolaryngoskopie (3)
- Volatile Anästhetika (3)
- airway management (3)
- analgesia (3)
- astrocytes (3)
- atrial fibrillation (3)
- caffeine (3)
- central nervous system (3)
- claudin-1 (3)
- electrical impedance tomography (3)
- gene expression (3)
- intensive care (3)
- iron deficiency (3)
- ischemia (3)
- macrophages (3)
- metabolic test (3)
- metabolischer Test (3)
- minimal invasiv (3)
- molecular dynamics (3)
- myocardial infarction (3)
- oxidative stress (3)
- oxygen/glucose deprivation (3)
- patient blood management (3)
- postoperative nausea and vomiting (3)
- pregnancy (3)
- skeletal muscle (3)
- systematic review (3)
- ventilation (3)
- Übelkeit (3)
- Alzheimer’s disease (2)
- Analgesie (2)
- Anästhesiologie (2)
- Anästhetika-induzierte Postkonditionierung (2)
- Anästhetika-induzierte Präkonditionierung (2)
- BK-Kanal (2)
- Beatmung (2)
- Blut-Nerven-Barriere (2)
- Blut-Nerven-Schranke (2)
- Blutverlust (2)
- Bupivacain (2)
- CNS disorders (2)
- Claudin (2)
- Claudin-1 (2)
- Claudine <Biologie> (2)
- Coronavirus (2)
- Covid-19 (2)
- Dünndarm (2)
- Dünndarmmotilität (2)
- ECMO-Therapie (2)
- Elektroimpedanztomographie (2)
- Endothel (2)
- Endotracheale Intubation (2)
- Erste Hilfe (2)
- Extracorporeal Membrane Oxygenation (2)
- Extrakorporale Membranoxygenierung (2)
- Geburtshilfe (2)
- Germany (2)
- HES (2)
- Hochfrequenz-Oszillations-Ventilation (2)
- Hydroxyethylstärke (2)
- Inflammation (2)
- Injury Severity Score (2)
- Intensivkapazitäten (2)
- Intubation (2)
- Ionenkanal (2)
- Ischämie (2)
- Ischämie/Reperfusionsschaden (2)
- Lactate (2)
- Laryngoskop (2)
- Laryngoskopie (2)
- Lungenfunktion (2)
- MK801 (2)
- Malignant hyperthermia (2)
- Metaanalyse (2)
- Metoprolol (2)
- Monitoring (2)
- NMDA-Antagonist (2)
- NMDA-Rezeptor (2)
- Narkoseeinleitung (2)
- Narkosezwischenfall (2)
- Nervenblockade (2)
- Nervenstimulation (2)
- Notfall (2)
- Operation (2)
- Opioide (2)
- Pandemie (2)
- Paracetamol (2)
- Patientengesteuerte Analgesie (2)
- Peristaltik (2)
- Phospholipide (2)
- Plexus brachialis (2)
- Proteasom (2)
- Pädiatrie (2)
- QST (2)
- Qualitätsmanagement (2)
- Reanimation (2)
- Remifentanil (2)
- Resuscitation (2)
- Rettungskette (2)
- Ropivacain (2)
- Schwangerschaft (2)
- Sectio caesarea (2)
- Sepsis (2)
- Spinalanästhesie (2)
- TRPA1 (2)
- Toll like receptors (2)
- Volumensubstitution (2)
- Volumentherapie (2)
- Wiederbelebung (2)
- ZO-1 (2)
- acetaminophen (2)
- acute lung injury (2)
- age-related hearing loss (2)
- aging (2)
- anaemia (2)
- anaesthesiology (2)
- analysis of variance (2)
- anesthetics (2)
- animal model (2)
- anticoagulation (2)
- antimicrobial stewardship (2)
- av-ECLA (2)
- barrier (2)
- blood (2)
- blood gas analysis (2)
- blood loss (2)
- blood nerve barrier (2)
- blood-nerve barrier (2)
- blood–labyrinth barrier (2)
- brain (2)
- bridging (2)
- cEND (2)
- capsaicin (2)
- cardiac surgery (2)
- cerebEND (2)
- chemokines (2)
- clinical trial (2)
- comparison (2)
- complex regional pain syndrome (2)
- critically ill (2)
- cytotoxicity (2)
- difficult airway (2)
- endotoxemia (2)
- etomidate (2)
- evaluation (2)
- exosomes (2)
- glioma (2)
- glucocorticoid receptor (2)
- glucocorticoids (2)
- heart failure (2)
- hyperalgesia (2)
- in vitro contracture test (2)
- inflammatory pain (2)
- ischemia-reperfusion injury (2)
- ischemia/reperfusion injury (2)
- lactate (2)
- lessons learned (2)
- lungenprotektive Beatmung (2)
- mRNA (2)
- mass casualties (2)
- medical nutrition therapy (2)
- meta-analysis (2)
- miRNS (2)
- mice (2)
- minimally invasive (2)
- mitochondrial permeability transition pore (2)
- monocytes (2)
- multidrug resistance (2)
- neuropathy (2)
- neurotrophins (2)
- pain therapy (2)
- perineurium (2)
- perioperative care (2)
- peristalsis (2)
- postoperative (2)
- postoperative bleeding (2)
- propofol (2)
- protein (2)
- randomized controlled trial (2)
- rat (2)
- resuscitation (2)
- rolipram (2)
- rtPA (2)
- safety (2)
- selenium (2)
- simulation (2)
- small intestine (2)
- spiral ganglion neuron (2)
- surgery (2)
- terror attack (2)
- therapy (2)
- thromboembolism (2)
- thrombosis (2)
- tight junction (2)
- ultrasound (2)
- video laryngoscopy (2)
- vitamin C (2)
- vitamin D (2)
- volatile Anästhetika (2)
- vomiting (2)
- zinc (2)
- (cardiac) surgery (1)
- 3D in vitro model (1)
- 4-HNE (1)
- 4D (1)
- 6-percent hydroxyethyl starch (1)
- ABC-Transporter (1)
- AD pathogenesis (1)
- AED (1)
- ANIMAX (1)
- APC (1)
- APD421 (1)
- ARDS (acute respiratory distress syndrome) (1)
- ATP-binding cassette transporter (1)
- Accelerometry (1)
- Acetylsalicylsäure (1)
- Acute Kidney Injury (1)
- Acute Respiratory Distress Syndrome (1)
- Adherens-Junction (1)
- Afferent nerve stimulation (1)
- Airtraq (1)
- Akutes Lungenversagen (1)
- Akutes Nierenversagen (1)
- Alarmierungsalgorithmus (1)
- Algorithmus (1)
- Allgemeinanästhesie (1)
- Alternative (1)
- Alzheimer's disease (1)
- Amisulprid Kombinationsprophylaxe (1)
- Amisulprid PONV (1)
- Analgesia (1)
- Analgetika (1)
- Animax (1)
- Anthocyane (1)
- Anthocyanidine (1)
- Antidepressiva (1)
- Antiinflammatory agents (1)
- Antikoagulation (1)
- Antikonvulsiva (1)
- Antineuropathika (1)
- Antinozizeption (1)
- Anwenderschulung (1)
- ApoA-I D-4F (1)
- Apoptosis (1)
- Apple Watch 7 (1)
- Articular afferent (1)
- Arztbegleiteter Patiententransport (1)
- Aspartate Aminotransferases (1)
- Assistierte Beatmung (1)
- Atemwegsmanagement (1)
- Audiovisuelle Medien (1)
- Augenbewegungen (1)
- Augenfolgebewegung (1)
- Ausstattung (1)
- AutoPulse (1)
- Autoantikörper (1)
- Automated External Defibrillators (1)
- Automatischer Externer Defibrillator (1)
- Autophagie (1)
- Autophagie <Physiologie> (1)
- Autophagy (1)
- Außerklinischer Herz-Kreislauf-Stillstand (1)
- Axl tyrosine kinase (1)
- Axonschaden (1)
- BDNF (1)
- BIRC7 (1)
- BIS (1)
- BK channel (1)
- BV-2 (1)
- Barriereeigenschaften (1)
- Bauchlage (1)
- Befindlichkeit (1)
- Behinderung (1)
- Berichterstattung (1)
- Beta-Rezeptor (1)
- Betaadrenerge Rezeptoren (1)
- Bias (1)
- Bland–Altman (1)
- Blood-Brain-Barrier (1)
- Blood–brain barrier (1)
- Blut-Luft-Schranke (1)
- Blut-Nerve-Schranke (1)
- Blut-Rückenmarkschranke (1)
- Blutgerinnung (1)
- Blutgerinnungshemmung (1)
- Blutvolumen (1)
- Bowel (1)
- Bradykinin (1)
- Breastcancer (1)
- Brustkrebs (1)
- C-MAC (1)
- C6 (1)
- CASP (1)
- CCL2 (1)
- CLP-Verfahren (1)
- CLP-procedure (1)
- CNS diseases (1)
- CNS injury (1)
- COVID 19 (1)
- COVID-19 pandemic (1)
- COVID-19-ARDS (1)
- COVID-19-Pademie (1)
- COVID‐19 (1)
- CPIP (1)
- CSM (1)
- CT (1)
- CX3CL1 (1)
- CXCL13 (1)
- CXCR4-targeting (1)
- Ca2+ homeostasis (1)
- Ca2+ ion analysis (1)
- Ca2+ leak (1)
- Ca2+ oscillation (1)
- CaM-Kinase II (1)
- Cadherine (1)
- Calcium Imaging (1)
- Calcium-Calmodulinkinase II (1)
- Capsaicin (1)
- Carrier-Proteine (1)
- Catecholamine (1)
- Catheter duration (1)
- Central venous-pressure (1)
- Cerebral Oxygen Saturation (1)
- Cerebral edema (1)
- Charmi-Index (1)
- Chemokin CXCL10 (1)
- Chest-Compression rate (1)
- Chirurgie (1)
- Cholesterintransporter (1)
- Chronische Schmerzen (1)
- Chronische Wunden (1)
- Claudin-12 (1)
- Claudin-5 (1)
- Claudine (1)
- ClearSight\(^®\) (1)
- Clusterkopfschmerz (1)
- Co-Analgetika (1)
- Cocamidopropylbetain (1)
- Cochrane Review (1)
- Coffein (1)
- Colloids (1)
- Complex regional pain syndrome (1)
- Complication (1)
- Computertomografie (1)
- Computertomographie (1)
- Conductance Katheter (1)
- Controlled cortical impact (1)
- Corona virus (1)
- Coronavirus Disease 2019 (1)
- Corticotropin-Releasing-Factor (1)
- Creatine Kinase (1)
- Critical Care (1)
- Critically-ill patients (1)
- Crystalloids (1)
- Cutaneous hyperemia (1)
- Cyclodextrine (1)
- D-4F (1)
- DAMGO (1)
- DRG (1)
- Darm (1)
- Darmmotilität (1)
- Darmmotilitätsstörung (1)
- Detergentien (1)
- Deutscher Schmerzfragebogen (1)
- Dexamethason (1)
- Diabetische Polyneuropathie (1)
- Diagnose (1)
- Dimethylsulfoxid (1)
- Disaster response (1)
- Dissertation (1)
- Dokumentationsqualität (1)
- Doppel-Ganzkörper-CT-Schockraum (1)
- Doppellumentubus (1)
- Dorsal Root Ganglion (1)
- Drug Targeting (1)
- Dünndarmfunktion (1)
- Dünndarmperistaltik (1)
- E06 mAb (1)
- ECLA (1)
- ECMO (1)
- ECMO indication (1)
- ECMO therapy (1)
- ELISA (1)
- ER Ca2+ imaging (1)
- ER Ca2+ store (1)
- Einfluss (1)
- Elastomere Schmerzpumpe (1)
- Elective cesarean-section (1)
- Electrical impedance tomography (1)
- Elektroakupunktur (1)
- Elektroencephalogramm (1)
- Emery-Dreifuss muscular dystrophy (1)
- Endogenous opioids (1)
- Endorphin (1)
- Endothelzelle (1)
- Endothelzelllinie (1)
- Enoxaparin (1)
- Entzündungsmodell (1)
- Epidural Analgesia (1)
- Epiduralanästhesie (1)
- Erk (1)
- Ernährungstherapie (1)
- Erwachsene (1)
- Ethanol (1)
- Etomidat (1)
- Evaluation (1)
- Everolimus (1)
- Exercise testing (1)
- Exosom <Vesikel> (1)
- Expertise (1)
- Expression (1)
- Extracorporeal life support (1)
- Extrakorporale kardiopulmonale Reanimation (1)
- Eye-Tracking (1)
- FIFA World Cup 2006 (1)
- Faktor V-Leiden (1)
- Fentanyl (1)
- Fibromyalgie (1)
- Fibromyalgiesyndrom (1)
- Fisher Z-score transformation (1)
- Fitbit Sense (1)
- Fluorchinolone (1)
- Fluorescence (1)
- Fluoreszenz (1)
- Fluoreszenzspektrometer (1)
- Formulierung (1)
- Fresh Freeze Plasma (1)
- GABA\(_A\) (1)
- GBM (1)
- GDNF (1)
- GRO alpha (1)
- Garmin Fenix 6 Pro (1)
- Geburt (1)
- Geburtshilfliche Intensivmedizin (1)
- Geburtsschmerz (1)
- Gene expression vectors (1)
- General anaesthesia (1)
- Geriatrie (1)
- German Pain Questionnaire (1)
- GlideScope-Videolaryngoskop (1)
- GlideScope-videolaryngoscope (1)
- Glucocorticosteroidrezeptor (1)
- Glucosetransport (1)
- Glucosetransportproteine (1)
- Glukokortikoide (1)
- Glutamin (1)
- Graphen (1)
- Gutmotility (1)
- H2O2 (1)
- HCW (1)
- HER2 conversion (1)
- HER2 targeted therapy (1)
- HER2-low (1)
- HIV (1)
- HK-2 Zellen (1)
- HPβCD (1)
- HUVEC (1)
- Halothane (1)
- Haltung (1)
- Hamman's syndrome (1)
- Healthcare Cost (1)
- Healthcare Economics (1)
- Helfer vor Ort (1)
- Hernie (1)
- Herzinfarktforschung (1)
- High-Frequency Ventilation (1)
- High-frequency oscillatory ventilation (1)
- High-volume-low-concentration-Technik (1)
- Hirnendothelzellen (1)
- Hirnkreislauf (1)
- Hirnmetastasen (1)
- Hirnschädigung (1)
- Hirnödem (1)
- Hochwasser (1)
- Horowitz Quotient (1)
- Hospital emergency plan (1)
- Humanalbumin (1)
- Hyberbaric oxygen therapy (1)
- Hydroxyethyl starch (1)
- Hydroxyäthylstärke (1)
- Hyperalgesie (1)
- Hypermetabolismus (1)
- Hypertonic saline 7.5-percent (1)
- Hypertonie (1)
- Hypovolämischer Schock (1)
- Hypoxie (1)
- HÄS (1)
- Hämatogene Oxidationstherapie (1)
- H�modynamik (1)
- ICU capacities (1)
- ICU staff (1)
- ICU treatment (1)
- IENFD (1)
- IL-6 (1)
- IL6 (1)
- ILA (1)
- IMA2.1 (1)
- INR rebound (1)
- ISS (1)
- ITW (1)
- IgG (1)
- IgG4 (1)
- IgY (1)
- Ileuseinleitung (1)
- Immunonutrition (1)
- Impedanztomografie (1)
- In Situ Nick-End Labeling (1)
- In Vitro Kontrakturtest (1)
- In vitro contracture test (1)
- In vitro models (1)
- In-hospital cardiac arrest (1)
- Induction of general anaesthesia (1)
- Infektionswellen (1)
- Inferior Vena Cava (1)
- Inflammatory Pain (1)
- Inflammatory pain (1)
- Inhalationsanaesthesien (1)
- Inhalationsnarkotikum (1)
- Intensivmedizin (1)
- Intensivpersonal (1)
- Intensivstation (1)
- Interactive Ventilatory Support (1)
- Interaktionsanalyse (1)
- Interdisziplinäre Schmerztherapie (1)
- Interhospitaltransfer (1)
- Interhospitaltransport (1)
- Interskalenäre Blockade (1)
- Intubationsschwierigkeiten (1)
- Intubationszeit (1)
- Inzidenz <Medizin> (1)
- Ischämische Postkonditionierung (1)
- Isosteviol-Natrium (1)
- Joint pain (1)
- Kaninchen (1)
- Karbonylierung (1)
- Katastrophe (1)
- Katastrophenschutz (1)
- Katecholamine (1)
- Katheterliegedauer (1)
- Knockout (1)
- Koffein (1)
- Kohlendioxidpartialdruckmessung (1)
- Kohlenstoffmonoxid (1)
- Kolloidale Volumenersatztherapie (1)
- Kombinationsprophylaxe PONV (1)
- Komplikation (1)
- Kontroll-Computertomografie (1)
- Krankenhausatlas (1)
- Kritische Infrastruktur (1)
- Künstliche Beatmung (1)
- Künstliche Lunge (1)
- L-Cystein (1)
- L-Lactate Dehydrogenase (1)
- L-cysteine (1)
- LPS (1)
- LRP1 (1)
- Labour Analgesia (1)
- Labour Pain (1)
- Lactated ringers solution (1)
- Laktat (1)
- Lamarckian genetic algorithms (1)
- Langerhans cells (1)
- Langzeitbeatmung (1)
- Lasermikrodissektion (1)
- Latrophilin (1)
- Leber (1)
- Lessons Learnt (1)
- Linksventrikuläre Funktionsparameter (1)
- Lokalanästhesie (1)
- Lokalanästhetikaintoxikation (1)
- Longitudinal analysis (1)
- Lucas CPR (1)
- Luftembolie (1)
- Lung Injury (1)
- Lunge (1)
- Lungenalveole (1)
- Lungenschädigung (1)
- Lungenultraschall (1)
- Lungprotective Ventilation (1)
- Luzindol Ileus (1)
- Lösungsmittel (1)
- MMP9 (1)
- Macintosh (1)
- Macintosh-Laryngoskop (1)
- Macintosh-laryngoscope (1)
- Macrophage Migration Inhibitory Factor (MIF) (1)
- Major abdominal surgery (1)
- Malignant Hyperthermia (1)
- Mammakarzinom (1)
- Mangansuperoxiddismutase (1)
- Mass critical care (1)
- Massenanfall (1)
- Medical Managment (1)
- Medizinische Fakultät (1)
- Medizinische Task Force (1)
- Melatonin (1)
- Memantin (1)
- Membranproteine (1)
- Metamizol (1)
- Metastatic breast cancer (1)
- Methohexital (1)
- Microcirculation (1)
- Microdialyse (1)
- Migräne (1)
- Minimal-invasive Chirurgie (1)
- Mitochondrien (1)
- Mobile intensive care unit (1)
- Mobilität (1)
- Monozyt (1)
- Monozyten (1)
- Motilitydysfunction (1)
- Myelin-Barriere (1)
- NCI H441 Zellen (1)
- NF-kappa-B (1)
- NMDAR (1)
- NRS-Skala (1)
- NS1608 (1)
- NSAIDs (1)
- NaV1.8 (1)
- Nahinfrarot-Spektroskopie (1)
- Nahinfrarotspektroskopie (1)
- Nanopartikel (1)
- Narkoseinduktion (1)
- Narkosetechnik (1)
- Narkosetiefe (1)
- Natrium/Glucose-Cotransporter (1)
- Natriumlaurylsulfat (1)
- Near-Infrared Spectroscopy (1)
- Neogenin-1 (1)
- Nephrotoxizität (1)
- Nerven (1)
- Netrin-1 (1)
- Neurogenie inflammation (1)
- Neurological complications (1)
- Neurologische Komplikationen (1)
- Neuromuscular disorders (1)
- Neuromuskuläre Erkrankungen (1)
- Neuropathic Pain (1)
- Neuropathic pain (1)
- Neuropathy (1)
- Neurotoxizität (1)
- Neutrophils (1)
- New Zealand (1)
- Nicardipine (1)
- Nicht-invasive Beatmung (1)
- Nierenversagen (1)
- Nitric oxide (NO) (1)
- Nociceptor (1)
- North American (1)
- Notarzt (1)
- OAA/S (1)
- OSC (1)
- Oberkörperhochlage (1)
- Obstetrics (1)
- Occludin (1)
- Omega-3-Fettsäure (1)
- Open-Lung-Beatmung (1)
- Open-lung-ventilation (1)
- Opioidsparender Effekt (1)
- Oxidized Phospholipids (1)
- Oxygen uptake (1)
- Oxygen-glucose deprivation (1)
- P-Welle (1)
- P-glycoprotein (1)
- P-gp inhibitors (1)
- PARs (1)
- PBM (1)
- PCA (1)
- PCDHGC3 (1)
- PCEA (1)
- PCIA (1)
- PCR (1)
- PDE4-inhibitor roflumilast (1)
- PEEP (1)
- PIK3R1 (1)
- POLO-chart (1)
- POLSCORE (1)
- Pain (1)
- Pain therapy (1)
- Patient (1)
- Patient Blood Management (PBM) (1)
- Patient Controlled Analgesia (1)
- Patient Satisfaction (1)
- Patientenaufnahme (1)
- Patiententransport (1)
- PcdhgC3 (1)
- Pearson correlation coefficient (1)
- Perineurium (1)
- Peroxisomen-Proliferator-aktivierter Rezeptor (1)
- Phase II trials (1)
- Phthalsäureester (1)
- Pim-1 Kinase (1)
- Polymerase chain reaction (1)
- Positive-Pressure Respiration (1)
- Post dural puncture headache (1)
- Postaggressorisches Syndrom (1)
- Postagressionsstoffwechsel (1)
- Postkonditionierung (1)
- Postkonditonierung (1)
- Postoperative Phase (1)
- Postoperative complications (1)
- Postoperatives Erbrechen (1)
- Postpunktionskopfschmerz (1)
- Predict fluid responsiveness (1)
- Pregnancy (1)
- Prilocain (1)
- Prognose (1)
- Prostacyclin (1)
- Prostaglandine (1)
- Proteinkinase A (1)
- Protocadherin gamma C3 (1)
- Protocadherine (1)
- Prozessqualität (1)
- Prädiktor (1)
- Präklinik (1)
- Pr�konditionierung (1)
- Psychologische Profile (1)
- Psychosoziale Belastung (1)
- Publikationsbias (1)
- Pulmonary Embolism (1)
- Pulmonary function tests (1)
- Puls-pressure variation (1)
- Quantitativ sensorische Testung (1)
- Quantitative sensory testing (1)
- Questionnaire (1)
- RECK (1)
- RSI (1)
- Randomized controlled-trial (1)
- Rapid Entire Body Assessment (1)
- Rapid Sequence Induction (1)
- Rapid sequence induction (1)
- Regional anesthesia (1)
- Regressionsanalyse (1)
- Reperfusion (1)
- Reperfusions-induzierter Schaden (1)
- Retrospektive Datenanalyse (1)
- Rettungshubschrauber (1)
- Risikofaktor (1)
- Risikoscore (1)
- RyR1 mutations (1)
- SARS-CoV2 (1)
- SARS-CoV‑2 (1)
- SERCA (1)
- SGLT (1)
- SIRS (1)
- SOFA Score (1)
- SOR (1)
- SUSTAIN CSX (1)
- SWCNT CNTs (1)
- Sanger sequencing (1)
- Sauerstoff (1)
- Sauerstoffkonzentration (1)
- Schmerztagesklinik (1)
- Schnittstelle (1)
- Schockraum (1)
- Schockraumbehandlung (1)
- Schockraummanagement (1)
- Schockraumteam (1)
- Schwefelwasserstoff (1)
- Selektive Endpunktberichterstattung (1)
- Serotonin (5-HT) (1)
- Severe Acute Respiratory Syndrome Coronavirus 2 (1)
- Shotgun method (1)
- Signaltransduktion (1)
- Siliciumdioxid (1)
- Simulation (1)
- Skelettmuskel (1)
- Sodium/glucose cotransporter (1)
- Sonografie (1)
- Spirometrie (1)
- Spumaviren (1)
- Starch volumetherapy nephrotoxicity HK-2 cells (1)
- Statine (1)
- Steroide (1)
- Stevia rebaudiana (1)
- Strain (1)
- Strainrate (1)
- Stress (1)
- Stress-Kardiomyopathie (1)
- Sturzflut (1)
- Succinylcholin (1)
- Sudeck (1)
- Sudeck-Syndrom (1)
- Sufentanil (1)
- Surgery (1)
- Swine (1)
- Synthetic biology (1)
- TNF-α (1)
- TRP channel (1)
- TRPA1 channel (1)
- TTFields (1)
- TTS (1)
- Takotsubo cardiomyopathy (1)
- Takotsubo syndrome (1)
- Takotsubo-Syndrom (1)
- Targeted drug delivery (1)
- Temperaturreiz (1)
- Terror (1)
- Thermodilution (1)
- Thorax (1)
- Thoraxkompressionsfrequenz (1)
- Thoraxröntgenbild (1)
- Thrombose (1)
- Tight Junction (1)
- Tight Junction Proteine (1)
- Tight Junction Proteins (1)
- Tight-Junction-Protein (1)
- Tjap1 (1)
- Toll-like Rezeptoren (1)
- Toxizität (1)
- Tramadol (1)
- Transfektion (1)
- Transwell® system (1)
- Transösophageale Ultraschallkardiographie (1)
- Traumatologie (1)
- Tumor-Treating Fields (TTFields) (1)
- Tyrian purple (1)
- UNC5B (1)
- USRA (1)
- Ultraschalldiagnostik (1)
- Ultraschallphantom (1)
- Ultraschallsichtbarkeit von Regionalanästhesienadeln (1)
- University Hospital (1)
- User Training (1)
- VACV (1)
- VILI (1)
- Vena jugularis interna (1)
- Venous Thrombosis (1)
- Vergleich (1)
- Verlegungsarzt (1)
- Verletzte (1)
- Verzerrung (1)
- Virtual sequencing (1)
- Visuelle Aufmerksamkeit (1)
- Volatile anesthetics (1)
- Volumenmanagement (1)
- Volumenregulation (1)
- Vomiting (1)
- WNT signaling (1)
- Wachheit (1)
- Weaning (1)
- Wehenschmerz (1)
- Wellenplan (1)
- Wirkspiegel (1)
- Withings ScanWatch (1)
- Wnt signaling (1)
- ZVK (1)
- ZVK-Lage (1)
- Zeitvorteil (1)
- Zell-Zell-Kontakte (1)
- Zellkontakt (1)
- Zellkultur (1)
- Zellkulturmodell (1)
- Zellskelett (1)
- Zerebrale Gewebeoxygenierung (1)
- Zika virus (1)
- Zufriedenheit (1)
- \(^1\)H-NMR spectroscopy (1)
- acetylsalicylic acid (1)
- activated-receptor gamma (1)
- activity-dependent slowing (1)
- acupuncture (1)
- acute Respiratory Distress Syndrome (1)
- acute liver failure (1)
- acute respiratory distress syndrome (ARDS) (1)
- adherens junction (1)
- adhesion molecules (1)
- admission capacity (1)
- adrenal tumor (1)
- adrenocortical cancer (1)
- adsorption (1)
- adultsPostoperatives Erbrechen ist ein häufiges und den Patienten belastendes Problem (1)
- aged 80 and over (1)
- aggregation (1)
- agnoists (1)
- air embolism (1)
- akutes Nierenversagen (1)
- alveolar epithelium in vitro model, claudin-1, claudin-3, claudin-4, claudin-5 (1)
- alzheimer's disease (1)
- amyloid cardiomyopathy (1)
- anaemia walk‐in clinic (1)
- anaesthesia (1)
- anaesthetics (1)
- analgesics (1)
- anesthesia (1)
- anesthesiologists (1)
- anesthesiology (1)
- anesthetic preconditioning (1)
- anesthetic-induced preconditioning (1)
- aneurysm repair (1)
- aneurysmal subarachnoid haemorrhage (1)
- angiogenesis (1)
- angioplasty (1)
- animals (1)
- anthocyanin derivatives (1)
- anti-cancer drug-like molecules (1)
- anti-hormonal therapy (1)
- antibacterial activity (1)
- antibiotic prescribing quality (1)
- anticoagulant therapy (1)
- antiemetic strategies (1)
- antiemetics (1)
- antiemetische Strategien (1)
- antioxidant (1)
- antioxidative Vitamine (1)
- antioxidative vitamins (1)
- antithrombotic therapy (1)
- anxiety (1)
- anästhetikainduzierte Präkonditionierung (1)
- apolipoprotein J (1)
- apoptosis (1)
- approved drugs (1)
- arteriovenous extracorporeal hemadsorption technique (1)
- artificial intelligence (1)
- astrocytoma (1)
- autoantibodies (1)
- autoimmun (1)
- autoimmune (1)
- autoimmune nodopathy (1)
- automated external defibrillators (1)
- autonomic nervous system (1)
- avoidable blood loss (1)
- awake prone positioning (1)
- awareness (1)
- axillary plexus (1)
- axillary plexus block (1)
- axilläre Plexusanästhesie (1)
- axonal damage (1)
- barrier properties (1)
- betaadrenergic receptors (1)
- bibliometrics (1)
- bioactive peptide (1)
- bioelectronics (1)
- biopsychosocial model of pain (1)
- biopsychosoziales Schmerzmodell (1)
- bleeding (1)
- blockchain anchoring (1)
- blockchain in healthcare (1)
- blockchain in the pharmaceutical industry (1)
- blockchain interoperability (1)
- blood CSF barrier (1)
- blood purification (1)
- blood transfusion (1)
- blood volume (1)
- blood–brain barrier choline transporter (1)
- bradykinin (1)
- brain endothelial cell line (1)
- brain pathology (1)
- brain-metastasis (1)
- breast cancer metastases (1)
- bupivacaine (1)
- c-fos (1)
- cEND-Zellen (1)
- calcitonin gene-related peptide (1)
- calcium level (1)
- calcium-activated potassium channel (1)
- calorimetry (1)
- cancer (1)
- carbon dioxide (1)
- carbon nanoparticles (1)
- carcinogen activation (1)
- cardiac arrest documentation (1)
- cardiac protection (1)
- cardio-pulmonary resuscitation (1)
- cardiopulmonary resuscitation (1)
- carrier proteins (1)
- caspase-3 (1)
- ceasarean section (1)
- cell stretch (1)
- cell-adhesion (1)
- central autonomic network (1)
- central core disease (1)
- cerebEND cells (1)
- cerebral ischemia (1)
- cerebral tissue oxygenation (1)
- cerebrospinal fluid (1)
- cerebrovascular disorders (1)
- chain-of-survival (1)
- chemical similarity (1)
- chest-compression rate (1)
- children (1)
- chronic constriction injury (1)
- chronic constriction nerve injury (1)
- chronic musculoskeletal pain (1)
- chronic wounds (1)
- chronisches Schmerzsyndrom (1)
- civil protection (1)
- claudin 1 (1)
- claudin-12 (1)
- claudin-5 (1)
- clinical decision support (1)
- clinical measurement in health technology (1)
- clinical studies (1)
- clinical trials (1)
- cluster headache (1)
- clusterin transporter (1)
- coagulation (1)
- cocamidopropylbetaine (1)
- colloids (1)
- colorectal carcinoma (1)
- comparative molecular field analysis (1)
- comparative molecular similarity index analysis (1)
- complex regional pain syndrom (1)
- complications (1)
- conductance catheter (1)
- conference abstracts (1)
- connective tissue (1)
- contactin (1)
- contracture test (1)
- core outcome set (1)
- coronary artery bypass (1)
- coronavirus disease 2019 (1)
- corticoid (1)
- corticosteroids (1)
- corticotropin-releasing-factor gut motility guinea pig (1)
- costs (1)
- creatinine (1)
- critical infrastructure (1)
- cut and sew technique (1)
- cvc (1)
- cyclodextrin (1)
- cyclodextrin formulations (1)
- cytochrome P450 3A4 (1)
- cytokine expression (1)
- data display (1)
- data harmonization (1)
- death (1)
- defibrillation (1)
- delivery (1)
- demography (1)
- density functional theory (1)
- depression (1)
- depth of anaesthesia (1)
- dermal B cells (1)
- dexamethasone (1)
- diabetes mellitus (1)
- diabetic nephropathy (1)
- diabetic retinopathy (1)
- diagnose (1)
- diagnostic blood loss (1)
- diagnostic correctness (1)
- diazepam (1)
- differentially expressed genes (1)
- diffusion (1)
- digital phenotyping (1)
- dimethylsulfoxide (1)
- dipyrone (1)
- disability (1)
- disease (1)
- diskontinuierlich (1)
- doctor in own practice (1)
- documentation quality (1)
- dorsal root ganglion (1)
- dose-dependency (1)
- driving pressure (1)
- drug delivery (1)
- drug delivery vector (1)
- drug repurposing (1)
- drug transporter (1)
- drug-drug interactions (1)
- dual-room trauma suite (1)
- dual-room whole-body CT (1)
- dysfunction (1)
- eCPR (1)
- ecological momentary assessment (1)
- electrical excitability (1)
- emergency (1)
- emergency first aid (1)
- emergency information (1)
- emergency medical aid (1)
- emergency preparedness (1)
- emesis (1)
- encephalitis dementia (1)
- endocarditis (1)
- endogenous opioids (1)
- endothelial injury (1)
- endothelium (1)
- endotoxin (1)
- endsystolic elastance (1)
- endsystolische Elastanz (1)
- enhanced recovery after surgery (1)
- enoxaparin (1)
- enzyme-linkes immunoassays (1)
- epidural anaesthesia (1)
- epidural analgesia (1)
- epidural anesthesia (1)
- epitheliae Barriere (1)
- equipment (1)
- erste Welle (1)
- estrogens (1)
- ethanol (1)
- ether (1)
- eudaimonia (1)
- evidence synthesis (1)
- exercise (1)
- exposure (1)
- extracellular vesicles (1)
- extracorporeal hemadsorption (1)
- extracorporeal membrane oxygenation (1)
- extracorporeal membrane oxygenation (ECMO) (1)
- extracorporeal techniques in hemadsorption therapy (1)
- extravascular lung water (1)
- factor v-Leiden (1)
- factorial design (1)
- failure (1)
- faktorielles Studiendesign (1)
- fascia (1)
- fears (1)
- femoral (1)
- fentanyl (1)
- fermentation (1)
- fetal lung (1)
- fibromyalgia (1)
- fibrosis (1)
- first responder (1)
- first responders (1)
- fish oil (1)
- fitness trackers (1)
- flooding (1)
- fluid therapy (1)
- fluorescein isothiocyanate (1)
- fluorescence microscopy (1)
- fluoroquinolones (1)
- formulations (1)
- frailty (1)
- free energy (1)
- free energy of solvation (1)
- free flap surgery (1)
- fullerenes (1)
- funktionell offenes Foramen ovale (1)
- gastrointestinal tract (1)
- gene ontology (1)
- general anaesthesia (1)
- general anesthesia (1)
- genetic polymorphisms (1)
- genotoxicity (1)
- giant ventral hernia (1)
- glioblastoma multiforme (1)
- glut1 (1)
- glutamine (1)
- glutathione peroxidase (1)
- good clinical practice (1)
- gradient optimisation (1)
- graft surgery (1)
- growth differentiation factor 15 (1)
- guanylyl cyclase (1)
- guideline adherence (1)
- guideline usage (1)
- guinea pig (1)
- gut motilty (1)
- gynäkologische Eingriffe (1)
- hCMEC/D3 (1)
- haemoglobin concentration (1)
- haemostasis (1)
- health care (1)
- health care payers (1)
- health care workers (1)
- health sciences (1)
- health tracker (1)
- health-care workers (1)
- healthcare (1)
- heart (1)
- hedonia (1)
- hemadsorption (1)
- high-flow nasal cannula (1)
- high-volume-low-concentration-technique (1)
- histopathology (1)
- hospital atlas (1)
- human (1)
- human brain microvascular endothelial cells (HBMVEC) (1)
- human cells (1)
- human factors (1)
- human immunodeficiency virus (1)
- humans (1)
- hydrochloride (1)
- hydrogen sulfide (1)
- hypertonic solution (1)
- hypovolemia (1)
- hypoxia (1)
- höheres Lebensalter (1)
- iatrogenic anemia (1)
- ileum (1)
- immortalization (1)
- immune response (1)
- immunology (1)
- immunonutrition (1)
- immunosorbents (1)
- immunostaining (1)
- impedance aggregometry; WHOLE-BLOOD THROMBOELASTOMETRY; DEFINITION; DISEASE (1)
- implementation (1)
- in vitro cell culture models (1)
- in vitro model (1)
- in vivo (1)
- in-bed cycling (1)
- in-hospital cardiac arrest (1)
- in-vitro Modellsystem (1)
- indigo (1)
- induced impairment (1)
- infiltration (1)
- inflammatory bowel disease (1)
- inflammatory cytokines (1)
- inflammatory neuropathy (1)
- inflammatory response (1)
- infodemic (1)
- information strategies (1)
- inguinal (1)
- inhalation anesthetics (1)
- inhalational anaesthesias (1)
- inhibition (1)
- injury severity score (1)
- inner ear (1)
- innerklinischer Herz-Kreislaufstillstand (1)
- innovative surgical methods (1)
- inos (1)
- insbesondere (1)
- insular cortex (1)
- intensive care medicine (1)
- intensive care transport (1)
- intensive care unit (1)
- interaction analysis (1)
- interhospital transfer (1)
- internalization (1)
- internet of things (1)
- interscalene block (1)
- intestinal absorption (1)
- intestinal microvascular perfusion (1)
- intestinal motility (1)
- intestine (1)
- intracerebral haemorrhage (1)
- intraoperativ (1)
- intubation (1)
- intubation time (1)
- involvement (1)
- ion channel (1)
- ion channels in the nervous system (1)
- iron deficiency anemia (1)
- ischemic preconditioning (1)
- isosteviol sodium (1)
- isosteviol sodium (STVNA) (1)
- kidney (1)
- kidney ischemia/reperfusion injury (1)
- kidneys (1)
- kontinuierlich und patientenkontrolliert (1)
- kritisch-kranke Patienten (1)
- laparoscopic surgery (1)
- laparostomy (1)
- laryngoscopy (1)
- laterality (1)
- left atrial appendage occlusion (1)
- left-ventricular assist device (1)
- leftventricular funktionparameters (1)
- levosimendan (1)
- lidocaine (1)
- lipids (1)
- livin (1)
- lnterleukin-lβ (1)
- logistic regression analysis (1)
- logistische Regressionsanalyse (1)
- long-term ventilation (1)
- longitudinal studies (1)
- low molecular heparin (1)
- low molecular heparine (1)
- low-molecular heparin (1)
- low-risk intra-abdominal infections (1)
- lps (1)
- lung function (1)
- lung injury (1)
- lung protective ventilation (1)
- lung ultrasound (1)
- machine learning (1)
- macrophage migration inhibitory factor (MIF) (1)
- major bleeding (1)
- malignant hyperthemia (1)
- management (1)
- mass casualty incident (1)
- mast cells (1)
- maternal critical care (1)
- mean force potential (1)
- meaning (1)
- mechanical power (1)
- mechanical ventilation (1)
- mechanical ventilator weaning (1)
- mechanisms (1)
- medical devices (1)
- medical task force (1)
- medicine (1)
- memantine (1)
- metablic test (1)
- metabolizing rate (1)
- metastasis (1)
- methohexital (1)
- methylprednisolone (1)
- metoprolol (1)
- miRNA (1)
- mices (1)
- microRNA-132 (1)
- microRNA-212 (1)
- microanastomosis (1)
- microarray (1)
- microglia (1)
- micronutrients (1)
- microparticles (1)
- microvascular complications (1)
- microvascular endothelial cells (1)
- midazolam (1)
- migraine (1)
- mikrodialysis (1)
- milk proteins (1)
- mimetic peptide (1)
- minimal invasive (1)
- minimal-invasiv (1)
- minimal-invasive (1)
- minimally invasive surgery (1)
- mission strategies (1)
- mitochondria (1)
- mobile crowdsensing (1)
- mobile health (1)
- moderate sedation (1)
- molecular imaging (1)
- molecular liphophilicity potential (1)
- molecular medicine (1)
- molecular modeling (1)
- molecular modelling (1)
- mortality (1)
- mouse models (1)
- movable sliding gantry (1)
- multidisciplinary (1)
- multimodal treatments (1)
- multiple sclerosis (1)
- multiwalled carbon nanotube (1)
- muscle (1)
- muscle disease (1)
- myelin barrier (1)
- myeloperoxidase (1)
- myocardial-infarction (1)
- myofibroblasts (1)
- myotonia congenita (1)
- nanomedicine (1)
- necrosis factor alpha (1)
- need satisfaction (1)
- nerve (1)
- nerve injury (1)
- nerve stimulation (1)
- nervestimulation (1)
- nervous system (1)
- netrin-1 (1)
- network meta-analysis (1)
- neurochirurgische Operation (1)
- neurofascin (1)
- neurofilament light chain (1)
- neurological complications (1)
- neurology (1)
- neuronal tracing (1)
- neuroprotection (1)
- neuropsychiatric disorders (1)
- neuroscience (1)
- neurosurgical operations (1)
- neurotrophic factor (1)
- neurovascular disorders (1)
- neurovasculature (1)
- neutrophil (1)
- niedergelassener Arzt (1)
- niedermolekulares Heparin (1)
- nitric oxide (1)
- no-flow fraction (1)
- nociception (1)
- nociceptive Schwann cells (1)
- node of ranvier (1)
- non-invasive ventilation (1)
- nutrient supplementation (1)
- nutrition (1)
- nutrition support (1)
- nutrition therapy (1)
- obstetrics (1)
- off-chain data (1)
- older adults (1)
- omega-3 fatty acid (1)
- omega-3-fatty acids (1)
- omega-6 fatty acid (1)
- one‐lung ventilation (1)
- open abdomen (1)
- opendsu (1)
- opioid peptides (1)
- opioid receptors (1)
- opioids (1)
- opioidsparing effect (1)
- optical laryngoscopes (1)
- optische Laryngoskope (1)
- oral anticoagulants (1)
- oral nutrition supplements (1)
- orthopaedic patients (1)
- out-of-hospital cardiac arrest (1)
- outcome reporting (1)
- oxidativer Stress (1)
- oxidised lipids (1)
- oxidized phospholipids (1)
- oxygen-glucose deprivation (1)
- p-wave (1)
- pCO2 (1)
- pain behavior (1)
- pain research (1)
- pain-related disability (1)
- pandemia (1)
- pandemic (1)
- parenteral analgesia (1)
- parenteral nutrition (1)
- passive transfer (1)
- patent foramen ovale (1)
- pathophysiology (1)
- patient (1)
- patient controlled analgesia (1)
- patient safety (1)
- patient serum (1)
- patient-controlled (1)
- patientenkontrollierte Analgesie (1)
- patients (1)
- paxilline (1)
- pediatric (1)
- peptide synthesis (1)
- performance (1)
- pericytes (1)
- perioperative Myokardischämien (1)
- perioperative antibiotic prophylaxis (1)
- perioperative myocardial ischemia (1)
- perioperative setting (1)
- peripartal (1)
- peripheral nerve (1)
- peripheral nerve injury (1)
- peripherer Nerv (1)
- permeability (1)
- peroxisome-proliferator-activated receptor (1)
- personalized antimicrobial therapy (1)
- personalized medicine (1)
- pharmaceutical applications (1)
- pharmacokinetic delivery (1)
- pharmacokinetics (1)
- pharmacology (1)
- pharmacotherapy (1)
- pharmaledger (1)
- phenprocoumon (1)
- phosphatidylinositol (1)
- phosphodiesterase (1)
- photoplethysmography (1)
- phthalates (1)
- physical activity (1)
- pi-pi stacking (1)
- pigs (1)
- pioglitazone (1)
- piperacillin/tazobactam (1)
- point of care testing (1)
- point-of-care (1)
- point-of-care-testing (1)
- polarization (1)
- polymers (1)
- polyneuropathy (1)
- polytrauma (1)
- population characteristics (1)
- position (1)
- positive pressure respiration (1)
- post-traumatic stress disorder (1)
- postconditioning (1)
- postoperativ (1)
- postoperative Nausea (1)
- postoperative complications (1)
- postoperative Übelkeit (1)
- postoperative Übelkeit und Erbrechen (1)
- postoperatives Befinden (1)
- predictor (1)
- prehabilitation (1)
- prehospital (1)
- preoperative anaemia management (1)
- preoperative setting (1)
- presynaptic inhibition (1)
- preterm birth (1)
- prevalence (1)
- prilocaine (1)
- primary endpoint (1)
- primary microvascular endothelial cells (1)
- primary outcome (1)
- prognostic marker (1)
- proliferation (1)
- propranolol (1)
- prospective studies (1)
- prostacyclin (1)
- prostaglandins (1)
- proteasome (1)
- protein corona (1)
- protein expression (1)
- protein hydrolysis (1)
- protein-protein interaction network (1)
- proteins (1)
- protocadherin gamma C3 (1)
- public health (1)
- public health preparedness (1)
- publication bias (1)
- pulmonary edema (1)
- pulmonary function tests (1)
- pulmonary surgical procedures (1)
- pulse therapy (1)
- punctate mechanical allodynia (1)
- qualitative research (1)
- quality assurance (1)
- quality indicators (1)
- quality of life (1)
- quantum mechanics (1)
- questionnaire (1)
- rabbits (1)
- randomized trial (1)
- rapid sequence induction (1)
- rational drug design (1)
- reactive oxygen species (1)
- receptor antagonist (1)
- receptors (1)
- recombinant DNA (1)
- recurrence (1)
- red blood cell transfusion (1)
- red blood cells (1)
- regional anesthesia (1)
- registry trial (1)
- relapse (1)
- reperfusion injury (1)
- repetitive firing (1)
- rescue mission (1)
- research integrity (1)
- resolvin (1)
- respiratory distress syndrome (1)
- respiratory failure (1)
- resuscitation time (1)
- reticulocyte haemoglobin (1)
- risk factor (1)
- risk prediction (1)
- risk score (1)
- robotic surgery (1)
- ropivacaine (1)
- ryanodine receptor gene (1)
- salvage therapy (1)
- sarcoplasmic reticulum (1)
- satisfaction (1)
- scaffold search (1)
- scanning electron microscopy (1)
- sceletal muscle (1)
- schmerzbedingte Beeinträchtigung (1)
- schwieriger Atemweg (1)
- sciatic nerve (1)
- scurvy (1)
- selective outcome reporting (1)
- selen (1)
- self-sovereign identities (1)
- senescence (1)
- sensory neurons (1)
- septic shock (1)
- serielle Computertomografie (1)
- severe multiple trauma (1)
- sex hormone (1)
- sglt1 (1)
- shape-based approach (1)
- sheep (1)
- side-effects (1)
- single-electron transistor (1)
- single-walled carbon nanotubes (1)
- sitting position (1)
- situation awareness (1)
- situational awareness (1)
- sitzende Lagerung (1)
- skin punch biopsy (1)
- smartwatch (1)
- smooth muscle cells (1)
- sodiumlaurylsulfate (1)
- solnatide (1)
- solvents (1)
- spinal anaesthesia (1)
- spinal dorsal horn (1)
- spontaneous pneumomediastinum (1)
- spontaneous pneumopericardium (1)
- sport medicine (1)
- statins (1)
- stent (1)
- store-operated Ca2+ entry (1)
- strain (1)
- strainrate (1)
- stress (1)
- stress resilience (1)
- structure-activity relationship (1)
- subarachnoid hemorrhage (1)
- succinylcholine (1)
- sudden flood (1)
- supine hypotensive syndrome (1)
- survey (1)
- susceptibility (1)
- suxamethonium (1)
- syndrome (1)
- synthetic mesh (1)
- systematic review, (1)
- systemic inflammatory response syndrome (1)
- systemic reviews (1)
- targeting (1)
- team-training (1)
- technology (1)
- terror attacks (1)
- theranostics (1)
- therapeutic antibody (1)
- therapeutic drug monitoring (1)
- therapiefreies Intervall (1)
- thermal threshold (1)
- thermodilution (1)
- three-dimensional quantitative structure–activity relationship (1)
- thromboelastometry (1)
- tight junction protein (1)
- tight junction proteins (1)
- time varying elastance (1)
- tissue resident T cells (1)
- torsional energy (1)
- trace elements (1)
- tramadol (1)
- transesophageal echocardiography (1)
- transfusion (1)
- transgenic mouse (1)
- transient receptor potential channels (1)
- transition state (1)
- transnasal TEE (1)
- transnasale TEE (1)
- transport inhibition assay (1)
- transporter (1)
- trastuzumab (1)
- trastuzumab deruxtecan (1)
- trauma centre (1)
- trauma management (1)
- trial protocol (1)
- trial registration (1)
- trimethyl-β-cyclodextrin (1)
- tumor (1)
- tumor microenvironment (1)
- tumor necrosis factor-α (1)
- ulfobutylether-\(\beta\)-cyclodextrin (1)
- ultrasound strain elastography (1)
- ultrastructure (1)
- urgent surgery (1)
- urine (1)
- urämische Enzephalopathie (1)
- user experience (1)
- user-centred design (1)
- vaccination (1)
- vaccination campaign (1)
- vaccination hesitancy (1)
- vaccine (1)
- vaccine hesitancy (1)
- vaccine refusal (1)
- vacuum conditioning (1)
- video-assisted laryngoscopy (1)
- viral load (1)
- virtual reality (1)
- virtual screening (1)
- viruses (1)
- vitamins (1)
- vitro contracture test (1)
- volume clamp (1)
- volunteer locally (1)
- warfarin interruption (1)
- water (1)
- weaning (1)
- wearable (1)
- white blood cells (1)
- wistar rats (1)
- x (1)
- x-ray (1)
- zentralvenöser Katheter (1)
- µ-Opioid receptor (1)
Institute
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (351) (remove)
Sonstige beteiligte Institutionen
- Zentrallabor, Universitätsklinikum Würzburg (2)
- Apotheke, Universitätsklinikum Würzburg (1)
- Department of Medicinal Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria (1)
- Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria (1)
- EMBL Mouse Biology Unit, Monterotondo, Italien (1)
- Interdisziplinäres Zentrum für Klinische Forschung (ZIKF), Würzburg (1)
- Klinik für Anästhesiologie, Universität Mainz (1)
- Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie des Universitätsklinikums Würzburg (1)
- Klinikum Fulda gAG (1)
- Krankenhaushygiene und Antimicrobial Stewardship (1)
Background: Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury.
Methods and Results: Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference -0.28 [-0.47, -0.09]).
Conclusion: There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin.
Fragestellung: Die Leberdysfunktion im Rahmen einer systemischen Inflammation stellt einen der wichtigsten Faktoren dar, welcher die Letalität erhöht. Sauerstoffradikale (ROS) sind zytotoxisch und wichtige Mediatoren in der Pathophysiologie der entzündlichen Leberschädigung. Dies war bereits Gegenstand vieler Arbeiten. Kohlenstoffmonoxid (CO), ein Produkt der Katalyse von Häm via Hämoxygenase (HO), wirkt zytoprotektiv gegen entzündliche Prozesse. In der vorliegenden Studie untersuchten wir in der Leber die Wirkungsweise von CO auf das Antioxidans Mangan-Superoxiddismutase (MnSOD) in einem Tiermodell der systemischen Entzündungsreaktion.
Methodik: Nach Einverständnis der Tierschutzkommission wurden männliche Mäuse (C57/BL6) mit Isoflurane narkotisiert und zur Messung des mittleren arteriellen Blutdruck (MAP) instrumentiert. Ein normotensives SIRS wurde mit Hilfe einer beidseitigen Ischämie der Hinterläufe für 60 Minuten und nachfolgender Reperfusion (I/R) für 3 Stunden induziert. Die Hämoxygenaseaktivität wurde mit Haem induziert und mittels Chromium Mesoporphyrin (CrMP) kompetetiv gehemmt. Ein Teil der Tiere inhalierte CO (250 ppm) nach Beginn der Reperfusion oder erhielt Methylenchlorid (MC, i.p.) zur Induktion der endogenen hepatischen CO Produktion. Die Fettsäurenoxidation (Malondialdehyde, MDA) und die Gewebespiegel für Glutathione (GSH) wurden mittels spezifischen Enzymessays bestimmt. ROS-Bildung konnte mittels intravitaler Fluoreszenzmikroskopie und dem Farbstoff Dihydrorhodamine (DHR) quantifiziert werden. Das Lebergewebe wurde in sinusoidale und parenchymale Zellfraktionen aufgetrennt. Die Mangan-Superoxiddismutase (MnSOD) Aktivität und Proteinmenge wurde in der sinusoidalen und parenchymalen Zellfraktion mittels Western Blot analysiert. Die Karbonylierung ist eine inaktivierende oxidative Proteinmodifikation. Das Ausmaß der Karbonylierung von MnSOD in den Zellfraktionen wurde mittels Immuno-Blot (OxyBlot; Chemicon) untersucht. Die statistische Testung erfolgte mittels Kruskal-Wallis Test, wobei p<0,05 signifikant war.
Ergebnisse: I/R Tiere zeigten signifikant mehr DHR-Fluoreszenz, mehr MDA-Bildung und weniger GSH als Sham Tiere (p<0.02). I/R+CrMP Behandlung hatte signifikant am meisten oxidativen Stress im Vergleich zu allen Behandlungsgruppen zur Folge. Die Inhalation von CO oder die Injektion von MC nach I/R reduzierte die DHR-Fluoreszenz, MDA-Bildung und normalisierte die GSH Spiegel im Vergleich zu I/R Tieren. I/R+CrMP+CO Behandlung zeigte die gleichen Ergebnisse wie I/R+CO Behandlung. Die parenchymale Zellfraktion der Leber zeigte keine Veränderung der MnSOD. In der sinusoidalen Zellfraktion fand sich keine Veränderung der MnSOD Proteinmenge. Jedoch reduzierte sich die sinusoidale MnSOD Aktivität signifikant nach I/R (p<0.02), erholte sich aber nach I/R+CO Behandlung wieder auf Sham Niveau. Die Karbonylierung von MnSOD nach I/R war signifikant erhöht in der sinusoidalen Zellfraktion. Nach I/R+CO konnte eine Reduktion der Karbonylierung von MnSOD auf das Sham Niveau nachgewiesen werden.
Interpretation: CO reduziert signifikant den hepatischen oxidativen Stress in der systemischen Inflammation. CO induziert die Aktivität der MnSOD in den sinusoidalen, nicht jedoch in den parenchymalen Zellen der Leber. Es konnte in der systemischen Entzündungsreaktion gezeigt werden, dass CO die antioxidative Wirkung von MnSOD durch eine Hemmung der Karbonylierung in den sinusoidalen Zellen der Leber induziert. Diese Ergebnisse zeigen erstmals, über die Karbonylierung von MnSOD, einen indirekten antioxidativen Effekt von CO. Welche weiteren Enzymsysteme von CO auf diese Weise beeinflusst werden, müssen weitere Untersuchungen zeigen.
Die Volumentherapie durch Infusionslösungen spielt eine herausragende Rolle im klinischen Alltag von Intensivmedizin, perioperativer Medizin und Notfallmedizin. Für diesen Zweck stehen verschiedene kristalloide und kolloidale Infusionslösungen zur Verfügung. Das in Deutschland am häufigsten eingesetzte Kolloid ist die Hydroxyethylstärke (HES). Dessen Stellenwert ist stark umstritten. Insbesondere die Wirkung von Hydroxyethylstärke auf die für den kritisch Kranken eine zentrale Rolle spielende Niere gilt als zentrales Problem. Die vorliegende Arbeit untersuchte aufbauend auf die in vivo-Versuche von Schick et al. die Auswirkungen klinisch relevanter Dosierungen von Hydroxyethylstärke und anderen Infusionslösungen (Gelatine, Humanalbumin, 0,9% NaCl, Sterofundin® ISO) auf die Viabilität von immortalisierten humanen proximalen Tubulusepithelzellen (HK-2). Im Anschluss wurde die Relevanz des pH - Wertes, der Osmolalität, der Trägerlösung, des Molekülursprungs, der Molekülgröße, der HES - Generation und der Inkubationsdauer auf die von HES ausgelösten Effekte geprüft. Danach wurde gezeigt, ob der beobachtete Effekt reversibel war, ob es sich um ein direkt zytotoxisches Phänomen handelte, ob die HES _ Wirkung durch proinflammatorische Stimuli verstärkt und ob HES selbst eine Inflammation auf mRNA - Ebene induzieren konnte. HES bewirkte keine proinflammatorische Stimulation der Zellen und wird durch die Anwesenheit proinflammatorischer Stimuli in seiner schädigenden Wirkung nicht verstärkt. Die mitochondriale Leistungsfähigkeit als Schlüsselaspekt des kritisch Kranken wurde durch den EZ4U („Viabilität“) bestimmt. Ein Messartefakt konnte nicht identifiziert werden. HES reduziert mit steigender Dosis die Viabilität der HK - 2 Zellen in deutlichem Ausmaß, obwohl die Zellen immortalisiert und nicht vorgeschädigt waren. Diese Reduktion erfolgte durch alle untersuchten HES - Präparate. Dabei war niedermolekulares HES leicht weniger schädlich als hochmolekulares HES. Der HES - Effekt war unmittelbar nach Beginn der Inkubation nachweisbar. Der Viabilitätsreduktion stand eine verzögert einsetzende Zytoxoxizität gegenüber. Der HES - Effekt war auch nach einer „Regenerationsphase“ der Zellen nachweisbar und somit in vitro nur partiell reversibel. Gelatine erwies sich im Vergleich als ebenso bis schlechter verträglich. Gelatine war deutlich zytotoxischer. Humanalbumin zeigte in niedrigen Dosierungen protektive, in hohen Dosierungen ebenfalls negative Einfluss auf Zellviabilität und war in höheren Dosierungen zytotoxisch. Die balancierte Vollelektrolytlösung Sterofundin® ISO war größtenteils inert, in seiner Wirkung auf die mRNA im Vergleich zur 0,9% NaCl Kontrolllösung protektiv. Zusammenfassend konnte eine Übergelegenheit des HES der „3. Generation“ gegenüber anderen HES - Präparaten nicht gefunden werden. Alles deutete darauf hin, dass ausschließlich die applizierte Gesamtmasse von HES ausschlaggebend ist. Synthetische Kolloide sind in vitro nephrotoxisch und beeinträchtigen die mitochondriale Funktionsf ähigkeit deutlich. Diese Beobachtungen entsprechen denen großer klinischer Studien. Die Ursache dieses Phänomens bleibt unklar. Weitere Grundlagenforschung ist notwendig, um den zugrundeliegenden Pathomechanimus aufzuklären.
Ischemia/reperfusion injury is a major cause of acute kidney injury (AKI). AKI is characterized by a sudden decrease in kidney function, systemic inflammation, oxidative stress, and dysregulation of the sodium, potassium, and water channels. While AKI leads to uremic encephalopathy, epidemiological studies have shown that AKI is associated with a subsequent risk for developing stroke and dementia. To get more insights into kidney–brain crosstalk, we have created an in vitro co-culture model based on human kidney cells of the proximal tubule (HK-2) and brain microvascular endothelial cells (BMEC). The HK-2 cell line was grown to confluence on 6-well plates and exposed to oxygen/glucose deprivation (OGD) for 4 h. Control HK-2 cells were grown under normal conditions. The BMEC cell line cerebED was grown to confluence on transwells with 0.4 μm pores. The transwell filters seeded and grown to confluence with cereEND were inserted into the plates with HK-2 cells with or without OGD treatment. In addition, cerebEND were left untreated or treated with uremic toxins, indole-3-acetic acid (IAA) and indoxyl sulfate (IS). The protein and mRNA expression of selected BBB-typical influx transporters, efflux transporters, cellular receptors, and tight junction proteins was measured in BMECs. To validate this in vitro model of kidney–brain interaction, we isolated brain capillaries from mice exposed to bilateral renal ischemia (30 min)/reperfusion injury (24 h) and measured mRNA and protein expression as described above. Both in vitro and in vivo systems showed similar changes in the expression of drug transporters, cellular receptors, and tight junction proteins. Efflux pumps, in particular Abcb1b, Abcc1, and Abcg2, have shown increased expression in our model. Thus, our in vitro co-culture system can be used to study the cellular mechanism of kidney and brain crosstalk in renal ischemia/reperfusion injury.
Epithelial and endothelial cells (EC) are building paracellular barriers which protect the tissue from the external and internal environment. The blood-brain barrier (BBB) consisting of EC, astrocyte end-feet, pericytes and the basal membrane is responsible for the protection and homeostasis of the brain parenchyma. In vitro BBB models are common tools to study the structure and function of the BBB at the cellular level. A considerable number of different in vitro BBB models have been established for research in different laboratories to date. Usually, the cells are obtained from bovine, porcine, rat or mouse brain tissue (discussed in detail in the review by Wilhelm et al. 1). Human tissue samples are available only in a restricted number of laboratories or companies 2,3. While primary cell preparations are time consuming and the EC cultures can differ from batch to batch, the establishment of immortalized EC lines is the focus of scientific interest.
Here, we present a method for establishing an immortalized brain microvascular EC line from neonatal mouse brain. We describe the procedure step-by-step listing the reagents and solutions used. The method established by our lab allows the isolation of a homogenous immortalized endothelial cell line within four to five weeks. The brain microvascular endothelial cell lines termed cEND 4 (from cerebral cortex) and cerebEND 5 (from cerebellar cortex), were isolated according to this procedure in the Förster laboratory and have been effectively used for explanation of different physiological and pathological processes at the BBB. Using cEND and cerebEND we have demonstrated that these cells respond to glucocorticoid- 4,6-9 and estrogen-treatment 10 as well as to pro-infammatory mediators, such as TNFalpha 5,8. Moreover, we have studied the pathology of multiple sclerosis 11 and hypoxia 12,13 on the EC-level. The cEND and cerebEND lines can be considered as a good tool for studying the structure and function of the BBB, cellular responses of ECs to different stimuli or interaction of the EC with lymphocytes or cancer cells.
Das Ziel dieser Studie war es, die Pathomechanismen der Enzepahlopathie, welche während einer akuten Nierenschädigung beobachtet werden kann, zu untersuchen. Wir konzipierten ein Zellkulturmodell, welches aus der cerebralen Endothelzelllinie cEND und der Nierentubuluszelllinie HK-2 bestant. Die Nierenzellen wurden einem Sauerstoff-Glukose-Entzug zugeführt, um eine akute Nierenschädigung zu simulieren. Nach weiterer Behandlung mit zwei urmämischen Toxinen (Indoxylsulfate und Indolessigsäure) und gemeinsamer Inkubation beider Zelllinien für insgesamt 48 Stunden wurden die cEND-Zellen geerntet und die Expression von Tight junction-Proteinen und Glukosetransportern untersucht.
Fragestellung: Experimentelle Ansätze zur selektiven Blockade von nozizeptiven Neuronen sind in vivo stark durch die Diffusionsbarriere des Perineuriums eingeschränkt, die das Vordringen von hydrophilen Substanzen zu ihrem Wirkort verhindert. Entscheidend für diese Barrierefunktion sind Tight Junctions zwischen Perineuralzellen, an deren Ausbildung das Transmembranprotein Claudin-1 beteiligt ist. In Vorarbeiten wurde gezeigt, dass die periphere Injektion einer 10 % NaCl-Lösung zur vorübergehenden Öffnung des Perineuriums führt. Dabei kommt es zur Freisetzung der Matrix-Metalloproteinase 9 (MMP9), die über Interaktion mit dem low density lipoprotein receptor-related protein 1 (LRP-1) Rezeptor eine Konzentrationsabnahme von Claudin-1 bewirkt. Durch perineurale Koinjektion von 10 % NaCl mit dem Opioidagonisten DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-Enkephalin) bzw. Tetrodotoxin ist damit im Verhaltensexperiment ein analgetischer Effekt auszulösen. Beobachtungen an der Blut-Hirn-Schranke konnten eine Öffnung über Interaktion von tPA mit LRP-1 zeigen. In dieser Studie sollten die Barriereöffnung sowie intrazelluläre Signalprozesse, die an der Öffnung des Perineuriums beteiligt sind, unter verschiedenen Bedingungen (hypertone NaCl-Lösung, MMP9 und tPA) charakterisiert werden.
Methodik: MMP9, 10 % NaCl-Lösung, tPA oder Erk Inhibitor (PD 98059) wurden mit Hilfe eines Nervenstimulators perineural an den N. ischiadicus von Wistar-Ratten injiziert. Danach wurden zu verschiedenen Zeitpunkten Nerven entnommen, um im Western Blot die Claudin-1 Expression in der Membranfraktion sowie die Phosphorylierung der intrazellulären Signalproteine Erk und Akt darzustellen. Nach perineuraler Injektion von tPA wurden in Schmerzverhaltenstests die Barriere öffnenden Wirkungen und immunhistochemisch und im Western Blot Auswirkungen auf die Konzentration von Claudin-1 und pErk untersucht.
Ergebnisse: Nach peripherer Injektion der 10 % NaCl-Lösung war über einen Zeitraum von 5-120 min eine Reduktion von Claudin-1 in der Membranfraktion und eine verstärkte Phosphorylierung von Erk nicht aber von Akt zu beobachten. Die Konzentrationszunahme von pErk wurde dabei nur im Perineurium, nicht im Nerveninneren nachgewiesen. Ebenso führte die periphere Injektion von MMP9 zu reduziertem Claudin-1 und einer verstärkten Phosphorylierung von Erk In Verhaltensexperimenten konnte gezeigt werden, dass die Injektion des Erk-Inhibitors PD98059 dosisabhängig zur Aufhebung der Antinozizeption führte, die nach Gabe von DAMGO in 10 % NaCl zu beobachten war. PD98059 blockierte den Abbau von Claudin-1 nach Injektion von 10 % NaCl. Perineurale Koinjektion von aktivem tPA (als LRP-1 Ligand) und DAMGO ermöglicht ebenfalls antinozizeptive Effekte. Immunhistochemisch und im Western Blot zeigte sich bei verschiedenen Dosierungen von aktivem tPA eine Konzentrationsabnahme von Claudin-1, eine verstärkte Phosphorylierung von Erk war jedoch nicht nachzuweisen. Nach Injektion von enzymatisch inaktiviertem tPA konnte nach einer Stunde keine Claudin-1 Konzentrationsänderung beobachtet werden.
Interpretation: Nach Injektion von 10 % NaCl kommt es zur verstärkten Phosphorylierung von Erk, die sich durch eine Interaktion der MMP9 Hemopexin- Domäne (MMP9-PEX) mit dem LRP-1 Rezeptor erklären lässt. Folge dieser Signalprozesse ist eine Konzentrationsabnahme von Claudin-1 und eine erhöhte Permeabilität des Perineuriums. Ähnlich zeigen erste Experimente auch nach Injektion von tPA eine Konzentrationsabnahme von Claudin. Damit bietet LRP-1 einen innovativen Angriffspunkt, um auch in vivo durch Öffnung des Perineuriums neue hydrophile Medikamente zur selektiven Blockade von Schmerzfasern zu nutzen.
Postoperative Übelkeit und postoperatives Erbrechen (PONV) sind eine der häufigsten und für Patient*innen unangenehmsten Nebenwirkungen einer Allgemeinanästhesie. Trotz jahrzehntelanger Forschung und der Vielfalt an mittlerweile bekannten Maßnahmen und Substanzen zur PONV-Prophylaxe und -Therapie gibt es noch keine Strategie, die eine sichere Vermeidung oder stets wirksame Therapie von PONV garantieren kann. In vorangegangenen Studien zeigte Amisulprid als Dopaminantagonist an den Rezeptortypen D2 und D3 vielversprechende Ergebnisse zur PONV-Prophylaxe und -Therapie.
Die dieser Arbeit zugrunde liegende prospektive, randomisierte, Placebo-kontrollierte Doppelblindstudie untersuchte die Wirksamkeit einer Einzeldosis APD421 5 mg bzw. 10 mg zur Therapie von manifestem PONV nach fehlgeschlagener PONV-Prophylaxe. „Complete Response“ (CR) wurde definiert als das Ausbleiben jeglicher weiterer emetischer Episoden im Zeitraum von 30 Minuten bis 24 Stunden nach Applikation des Studienmedikaments sowie keine Gabe von antiemetischer Rescue-Medikation im gesamten Zeitraum bis 24 Stunden nach Applikation des Studienmedikaments. Die CR-Raten lagen bei 41,7% für APD421 10 mg, 33,8% für APD421 5 mg und 28,5% für Placebo, wobei die Studienarme jeweils 230, 237 bzw. 235 Patient*innen umfassten. Eine Dosis APD421 10 mg zeigte somit statistisch signifikante Überlegenheit in der PONV-Therapie gegenüber Placebo. Auch hinsichtlich sekundärer Studienendpunkte wie Auftreten bzw. Stärke von Übelkeit, Würgen oder Erbrechen und Bedarf an Rescue-Medikation war APD421 10 mg gegenüber Placebo überlegen. Eine Dosis von 5 mg APD421 zeigte für die meisten Endpunkte hingegen keine statistisch signifikante Überlegenheit gegenüber Placebo.
Limitationen der Studie liegen im Ausschluss von Patientengruppen wie beispielsweise Kindern oder bestimmten Vorerkrankungen und dem mit über 90% sehr hohen Anteil weiblicher Patient*innen. Es bleiben weitere Studien abzuwarten, die APD421 einem direkten Vergleich mit bislang etablierten Substanzen zur PONV-Therapie unterziehen, um den künftigen Stellenwert der Substanz im klinischen Alltag einschätzen zu können.
The blood–nerve barrier and myelin barrier normally shield peripheral nerves from potentially harmful insults. They are broken down during nerve injury, which contributes to neuronal damage. Netrin-1 is a neuronal guidance protein with various established functions in the peripheral and central nervous systems; however, its role in regulating barrier integrity and pain processing after nerve injury is poorly understood. Here, we show that chronic constriction injury (CCI) in Wistar rats reduced netrin-1 protein and the netrin-1 receptor neogenin-1 (Neo1) in the sciatic nerve. Replacement of netrin-1 via systemic or local administration of the recombinant protein rescued injury-induced nociceptive hypersensitivity. This was prevented by siRNA-mediated knockdown of Neo1 in the sciatic nerve. Mechanistically, netrin-1 restored endothelial and myelin, but not perineural, barrier function as measured by fluorescent dye or fibrinogen penetration. Netrin-1 also reversed the decline in the tight junction proteins claudin-5 and claudin-19 in the sciatic nerve caused by CCI. Our findings emphasize the role of the endothelial and myelin barriers in pain processing after nerve damage and reveal that exogenous netrin-1 restores their function to mitigate CCI-induced hypersensitivity via Neo1. The netrin-1-neogenin-1 signaling pathway may thus represent a multi-target barrier protector for the treatment of neuropathic pain.
Volatile anesthetic-induced preconditioning ( APC) has shown to have cardiac and cerebral protective properties in both pre-clinical models and clinical trials. Interestingly, accumulating evidences demonstrate that, except from some specific characters, the underlying molecular mechanisms of APC-induced protective effects in myocytes and neurons are very similar; they share several major intracellular signaling pathways, including mediating mitochondrial function, release of inflammatory cytokines and cell apoptosis. Among all the experimental results, cortical spreading depolarization is a relative newly discovered cellular mechanism of APC, which, however, just exists in central nervous system. Applying volatile anesthetic preconditioning to clinical practice seems to be a promising cardio- and neuroprotective strategy. In this review, we also summarized and discussed the results of recent clinical research of APC. Despite all the positive experimental evidences, large-scale, long-term, more precisely controlled clinical trials focusing on the perioperative use of volatile anesthetics for organ protection are still needed.
Simple Summary
Anti-hormonal therapie regimes are well established in oncological treatments in breast cancer. In contrast there is limited knowledge of their effects on metastatic brain metastases in advanced breast cancer and their ability to cross the blood brain-barrier. In this review, we point out the usual antihormonal therapy options in the primary disease, but also in metastatic breast cancer. In addition, we explain the epidemiological facts of brain metastases, as well as the basics of the blood-brain barrier and how this is overcome by metastase. Last but not least, we deal with the known anti-hormonal therapy options and present clinical studies on their intracerebral effect, as well as the known basics of their blood-brain barrier penetration. Not all common anti-hormonal therapeutics are able to penetrate the CNS. It is therefore important for the treating oncologists to use substances that have been proven to cross the BBB, despite the limited data available. Aromataseinhibitors, especially letrozole, probably also tamoxifen, everolimus and CDK4/6 inhibitors, especially abemaciclib, appear to act intracerebrally by overcoming the blood-brain barrier. Nevertheless, further data must be obtained in basic research, but also health care research in relation to patients with brain metastases.
Abstract
The molecular receptor status of breast cancer has implications for prognosis and long-term metastasis. Although metastatic luminal B-like, hormone-receptor-positive, HER2−negative, breast cancer causes brain metastases less frequently than other subtypes, though tumor metastases in the brain are increasingly being detected of this patient group. Despite the many years of tried and tested use of a wide variety of anti-hormonal therapeutic agents, there is insufficient data on their intracerebral effectiveness and their ability to cross the blood-brain barrier. In this review, we therefore summarize the current state of knowledge on anti-hormonal therapy and its intracerebral impact and effects on the blood-brain barrier in breast cancer.
Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.
Background
The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breast cancer into the brain is the migration of cancer cells across the blood-brain barrier (BBB).
Methods
We adapted and validated the CD34\(^+\) cells-derived human in vitro BBB model (brain-like endothelial cells, BLECs) to analyse the effects of patient serum on BBB properties. We collected serum samples from healthy donors, breast cancer patients with primary cancer, and breast cancer patients with, bone, visceral or cerebral metastases. We analysed cytokine levels in these sera utilizing immunoassays and correlated them with clinical data. We used paracellular permeability measurements, immunofluorescence staining, Western blot and mRNA analysis to examine the effects of patient sera on the properties of BBB in vitro.
Results
The BLECs cultured together with brain pericytes in transwells developed a tight monolayer with a correct localization of claudin-5 at the tight junctions (TJ). Several BBB marker proteins such as the TJ proteins claudin-5 and occludin, the glucose transporter GLUT-1 or the efflux pumps PG-P and BCRP were upregulated in these cultures. This was accompanied by a reduced paracellular permeability for fluorescein (400 Da). We then used this model for the treatment with the patient sera. Only the sera of breast cancer patients with cerebral metastases had significantly increased levels of the cytokines fractalkine (CX3CL1) and BCA-1 (CXCL13). The increased levels of fractalkine were associated with the estrogen/progesterone receptor status of the tumour. The treatment of BLECs with these sera selectively increased the expression of CXCL13 and TJ protein occludin. In addition, the permeability of fluorescein was increased after serum treatment.
Conclusion
We demonstrate that the CD34\(^+\) cell-derived human in vitro BBB model can be used as a tool to study the molecular mechanisms underlying cerebrovascular pathologies. We showed that serum from patients with cerebral metastases may affect the integrity of the BBB in vitro, associated with elevated concentrations of specific cytokines such as CX3CL1 and CXCL13.
This work investigated phenotypes of complex regional pain syndrome (CRPS) with special interest in sensory abnormalities. Quantitative sensory testing (QST) was used to assess sensory function. In addition, clinical and sensory differences of fracture and CRPS patients were addressed. Finally, the longitudinal outcome of CRPS patients was part of this thesis.
Purpose
Once open abdomen therapy has succeeded, the problem of closing the abdominal wall must be addressed. We present a new four-stage procedure involving the application of a two-component mesh and vacuum conditioning for abdominal wall closure of even large defects. The aim is to prevent the development of a giant ventral hernia and the eventual need for the repair of the abdominal wall.
Methods
Nineteen of 62 patients treated by open abdomen over a two-year period could not receive primary abdominal wall closure. To achieve closure in these patients, we applied the following four-stage procedure: stage 1: abdominal damage control and conditioning of the abdominal wall; stage 2: attachment of a tailored two-component mesh of polyglycolic acid (PGA) and large pore polypropylene (PP) in intraperitoneal position (IPOM) plus placement of a vacuum bandage; stage 3: vacuum therapy for 3–4 weeks to allow granulation of the mesh and optimization of dermatotraction; stage 4: final skin suture. During stage 3, eligible patients were weaned from respirator and mobilized.
Results
The abdominal wall gap in the 19 patients ranged in size from 240 cm2 to more than 900 cm2. An average of 3.44 vacuum dressing changes over 19 days were required to achieve 60–100 % granulation of the surface area, so final skin suture could be made. Already in stage 3, 14 patients (73.68 %) could be weaned from respirator an average of 6.78 days after placement of the two-component mesh; 6 patients (31.57 %) could be mobilized on the edge of the bed and/or to a bedside chair after an average of 13 days. No mesh-related hematomas, seromas, or intestinal fistulas were observed.
Conclusion
The four-stage procedure presented here is a viable option for achieving abdominal wall closure in patients treated with open abdomen, enabling us to avoid the development of planned giant ventral hernias. It has few complications and has the special advantage of allowing mobilization of the patients before final skin closure. Long-term course in a large number of patients must still confirm this result.
Protocadherine spielen eine wichtige Rolle bei der Entwicklung des Nervensystems und sind an Prozessen der Zellmigration und -differenzierung, sowie der Hemmung von Zellwachstum beteiligt.
Um die Funktion und Regulation von Protocadherin gamma C3 (PcdhγC3) an mikrovaskulären Endothelzellen des Großhirns (cEND) und des Kleinhirns (cerebEND) zu untersuchen, wurden die PcdhγC3-Knock-out (KO) Zelllinien mit der CRISPR/Cas9 Methode etabliert.
Der KO führt zu verminderten Barriereeigenschaften der Blut-Hirn-Schranke (BHS), was sich in einer erhöhten Permeabilität für Fluoreszein und einem verringerten transendothelialen elektrischen Widerstand (TEER) widerspiegelt.
Es konnte eine Veränderung der Wachstumsrate und dem Adhäsionsverhalten der KO-Zellen nachgewiesen werden. Auch die Expression der Tight-Junction-Proteine, sowie einiger Komponenten des Wnt und mTOR Signalwegs wurden durch den KO von PcdhgC3 beeinflusst.
In 1747, an important milestone in the history of clinical research was set, as the Scottish surgeon James Lind conducted the first randomized controlled trial. Lind was interested in scurvy, a severe vitamin C deficiency which caused the death of thousands of British seamen. He found that a dietary intervention with oranges and lemons, which are rich in vitamin C by nature, was effective to recover from scurvy. Because of its antioxidative properties and involvement in many biochemical processes, the essential micronutrient vitamin C plays a key role in the human biology. Moreover, the use of vitamin C in critical illness—a condition also resulting in death of thousands in the 21st century—has gained increasing interest, as it may restore vascular responsiveness to vasoactive agents, ameliorate microcirculatory blood flow, preserve endothelial barriers, augment bacterial defense, and prevent apoptosis. Because of its redox potential and powerful antioxidant capacity, vitamin C represents an inexpensive and safe antioxidant, with the potential to modify the inflammatory cascade and improve clinical outcomes of critically ill patients. This narrative review aims to update and provide an overview on the role of vitamin C in the human biology and in critically ill patients, and to summarize current evidence on the use of vitamin C in diverse populations of critically ill patients, in specific focusing on patients with sepsis and coronavirus disease 2019.
Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness.
Hintergrund:
Eine adäquate Schmerztherapie ist eine zentrale Aufgabe der geburtsbegleitenden Anästhesie.
Ziel der Sekundäranalyse der prospektiven Längsschnittstudie war es, herauszufinden, ob es Variablen gibt, in denen sich Frauen unterscheiden, die mit der peripartalen Schmerztherapie zufrieden bzw. weniger zufrieden sind bzw. den Wunsch nach mehr Schmerzmitteln äußern oder nicht äußern.
Methodik:
Um dies herauszufinden wurden 210 Frauen vor Geburt (T1), kurz nach Geburt (T2) sowie drei (T3) und sechs Monate (T) postpartal bezüglich ihrer Zufriedenheit/ ihres Wunschs nach mehr Schmerzmitteln befragt. Des Weiteren wurden Daten zu Demographie, Schmerzmitteleinnahme, Geburtsablauf u.v.m. sowie Daten aus verschiedenen, psychologischen Fragebögen ermittelt. Die Auswertung der Daten konzentrierte sich auf die Erhebungszeitpunkte T1 und T2.
Ergebnisse:
Am ersten postpartalen Tag nach Kaiserschnitt zeigten sich sehr hohe Schmerzintensitäten (mediane Schmerzintensität bei Belastung: 8). Auffallend war, dass sowohl zu T1 als auch zu T2 eine erfolgreiche Schmerzlinderung beide Variablen signifikant beeinflusste, unabhängig davon, ob die Frauen trotz Schmerzlinderung noch starke Schmerzen hatten. 28% der Frauen erhielten nach Sectio retardierte Opioide jedoch blieb die Zufriedenheit und der Wunsch nach mehr Schmerzmitteln davon unbeeinflusst. Der Grund für die Ergebnisse bleibt unklar, könnte aber in möglichen Nebenwirkungen oder Vorbehalten gegenüber pharmakologischen Analgetika liegen. Beim präpartal durchgeführten PCS-Fragebogen waren Frauen mit Kaiserschnitt, die eine erhöhte Punktezahl aufwiesen, zum Zeitpunkt T2 signifikant unzufriedener und äußerten häufiger den Wunsch nach mehr Schmerzmittel.
Diskussion:
Die Ergebnisse weisen darauf hin, dass eine präpartale Erhebung von Risikofaktoren, wie z.B. erhöhte Werte auf der PCS-Skala ein Instrument sein könnte, um die Zufriedenheit mit der peripartalen Schmerztherapie zu verbessern. Patientinnen mit Risikofaktoren könnten so intensiver betreut werden, durch eine multimodale Therapie in Form von intensivierter Analgesie, aber z.B. auch durch eine psychologische Begleitung oder alternative Methoden zur Schmerzreduktion. Die erhaltene Schmerzlinderung präsentierte sich als wesentliche Einflussgröße auf die Zufriedenheit und den Wunsch nach mehr Schmerzmittel und ist somit womöglich zur Kontrolle des Therapieerfolgs besser geeignet als die alleinige Angabe der aktuellen Schmerzen.
Background
Perioperative bridging of oral anticoagulation increases the risk of bleeding complications after elective general and visceral surgery. The aim of this study was to explore, whether an individual risk-adjusted bridging regimen can reduce bleeding events, while still protecting against thromboembolic events.
Methods
We performed a quality improvement study comparing bridging parameters and postoperative outcomes before (period 1) and after implementation (period 2) of a new risk-adjusted bridging regimen. The primary endpoint of the study was overall incidence of postoperative bleeding complications during 30 days postoperatively. Secondary endpoints were major postoperative bleeding, minor bleeding, thromboembolic events, postoperative red blood cell transfusion, perioperative length-of-stay (LOS) and in-hospital mortality.
Results
A total of 263 patients during period 1 and 271 patients during period 2 were compared. The included elective operations covered the entire field of general and visceral surgery. The overall incidence of bleeding complications declined from 22.1% during period 1 to 10.3% in period 2 (p < 0.001). This reduction affected both major as well as minor bleeding events (8.4% vs. 4.1%; p = 0.039; 13.7% vs. 6.3%; p = 0.004). The incidence of thromboembolic events remained low (0.8% vs. 1.1%). No changes in mortality or length-of-stay were observed.
Conclusion
It is important to balance the individual thromboembolic and bleeding risks in perioperative bridging management. The risk adjusted bridging regimen reduces bleeding events in general and visceral surgery while the risk of thromboembolism remains comparably low.