Refine
Has Fulltext
- yes (349)
Is part of the Bibliography
- yes (349)
Year of publication
Document Type
- Journal article (193)
- 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)
- pain (7)
- stroke (7)
- Anästhesie (6)
- Desfluran (6)
- Entzündung (6)
- Erbrechen (6)
- Herzinfarkt (6)
- PONV (6)
- Präkonditionierung (6)
- SARS-CoV-2 (6)
- Schmerzforschung (6)
- cytokines (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)
- 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)
- 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 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)
- 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)
- 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 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)
- 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)
- 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)
- 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)
- 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) (349) (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)
Malignant hyperthermia is a rare but life-threatening complication of general anesthesia in predisposed patients usually triggered by potent inhalation anesthetics and/or the depolarizing muscle relaxant succinylcholine. The authors present a case of delayed sevoflurane-induced malignant hyperthermia in a 21-year-old male patient that was sufficiently treated by discontinuation of trigger agent application and dantrolene infusion. After surviving an MH episode diagnostic procedures are indicated to increase patient safety. In the presented case, the use of a novel minimal-invasive metabolic test with intramuscular injection of halothane and caffeine successfully confirmed MH susceptibility and hence might be an alternative for invasive in vitro contracture testing in selected cases.
Background: Over the recent years, technological advances of wrist-worn fitness trackers heralded a new era in the continuous monitoring of vital signs. So far, these devices have primarily been used for sports.
Objective: However, for using these technologies in health care, further validations of the measurement accuracy in hospitalized patients are essential but lacking to date.
Methods: We conducted a prospective validation study with 201 patients after moderate to major surgery in a controlled setting to benchmark the accuracy of heart rate measurements in 4 consumer-grade fitness trackers (Apple Watch 7, Garmin Fenix 6 Pro, Withings ScanWatch, and Fitbit Sense) against the clinical gold standard (electrocardiography).
Results: All devices exhibited high correlation (r≥0.95; P<.001) and concordance (rc≥0.94) coefficients, with a relative error as low as mean absolute percentage error <5% based on 1630 valid measurements. We identified confounders significantly biasing the measurement accuracy, although not at clinically relevant levels (mean absolute error<5 beats per minute).
Conclusions: Consumer-grade fitness trackers appear promising in hospitalized patients for monitoring heart rate.
Background
Enteric glial cells (EGCs) are the main constituent of the enteric nervous system and share similarities with astrocytes from the central nervous system including their reactivity to an inflammatory microenvironment. Previous studies on EGC pathophysiology have specifically focused on mucosal glia activation and its contribution to mucosal inflammatory processes observed in the gut of inflammatory bowel disease (IBD) patients. In contrast knowledge is scarce on intestinal inflammation not locally restricted to the mucosa but systemically affecting the intestine and its effect on the overall EGC network.
Methods and Results
In this study, we analyzed the biological effects of a systemic LPS-induced hyperinflammatory insult on overall EGCs in a rat model in vivo, mimicking the clinical situation of systemic inflammation response syndrome (SIRS). Tissues from small and large intestine were removed 4 hours after systemic LPS-injection and analyzed on transcript and protein level. Laser capture microdissection was performed to study plexus-specific gene expression alterations. Upon systemic LPS-injection in vivo we observed a rapid and dramatic activation of Glial Fibrillary Acidic Protein (GFAP)-expressing glia on mRNA level, locally restricted to the myenteric plexus. To study the specific role of the GFAP subpopulation, we established flow cytometry-purified primary glial cell cultures from GFAP promotor-driven EGFP reporter mice. After LPS stimulation, we analyzed cytokine secretion and global gene expression profiles, which were finally implemented in a bioinformatic comparative transcriptome analysis. Enriched GFAP+ glial cells cultured as gliospheres secreted increased levels of prominent inflammatory cytokines upon LPS stimulation. Additionally, a shift in myenteric glial gene expression profile was induced that predominantly affected genes associated with immune response.
Conclusion and Significance
Our findings identify the myenteric GFAP-expressing glial subpopulation as particularly susceptible and responsive to acute systemic inflammation of the gut wall and complement knowledge on glial involvement in mucosal inflammation of the intestine.
In cats anesthetized with alpha-chloralose, extracellular recordings were made from fine afferent units belonging to the medial articular nerve (MAN) of the knee joint. The excitatory and sensitizing effects on articular afferents of serotonin (5-HT) applied intra-arterially close to the joint were examined. The joints were either normal or an experimental arthritis had been induced some hours before the recording session. Bolus injections of 1.35-135 p,g 5-HT excited about 43% of group 111 (CV: 2.5-20 m/sec) and 73% of group IV units (CV: < 2.5 mjsec) from normal joints. The latency was usually between 10 and 30 sec, and the duration and size of the responses were dose-dependent. Fast group 111 units (CV: > 16 mjsec) and group li units (CV: > 20 m/sec) were never excited by 5-HT. Repetitiveadministration led to pronounced tachyphylaxis of the 5-HT response. Inflammation induced an enhanced sensitivity of group III articular afferent units to close intra-arterial application of 5-HT. In particular the total duration of each response was considerably prolonged (4-10 min against 1-2 min under normal conditions). At the same time the tachyphylaxis seen under normal conditions was gteatly reduced. In contrast, group IV articular afferent units did not become sensitized to 5-HT in the course of inflammation. In normal joints 5-HT did not sensitize fineafferent units for movement-induced responses. However, after inflammation, a distinct sensitization to such movements by 5-HT application could be observed bothin group 111 and group IV fiber ranges. The sensitization had a short time course not exceeding 7 min. The tonic component of the movement-induced response was more enhanced than the phasic one. The bolus application of 5-HT led to temporary vasoconstriction of the knee joint vessels. This vasoconstriction was especially pronounced in inflamed joints and impeded the access of subsequently applied substances to the terminal regions of the afferent units under observation. lt is concluded that the present results support the notion that 5-HT may participate in the mediation of pain from inflamed tissue such as an arthritic joint by exciting and sensitizing fine afferent units. During inflammation group 111 units are particularly sensitive to 5-HT and, thus, may carry the bulk of the 5-HT-induced nociceptive messages.
During stroke the blood–brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non-competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7- fold after 6 h OGD, which was significantly reduced by 10 μM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907% after 6 h OGD and was still higher (210%) after the 20 h reoxygenation phase compared to normoxia. Ten micromolar MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells.
Background
The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration.
Methods
Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials.
Results
Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62–0.97, p = 0.03; I2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference − 3.13 days, 95% CI − 5.36 to − 0.89, n = 1250, p = 0.006; I2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference − 5.07 days, 95% CI − 7.42 to − 2.73, n = 572, p < 0.0001; I2 = 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels.
Conclusions
Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results.
Advances in breast cancer management and extracellular vesicle research, a bibliometric analysis
(2021)
Extracellular vesicles transport variable content and have crucial functions in cell–cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, we aimed to investigate the trends in breast cancer management involved with extracellular vesicle research. Articles were retrieved from Scopus, including all the documents published concerning breast cancer and extracellular vesicles. We analyzed authors, journals, citations, affiliations, and keywords, besides other bibliometric analyses, using R Studio version 3.6.2. and VOSviewer version 1.6.0. A total of 1151 articles were retrieved, and as the main result, our analysis revealed trending topics on biomarkers of liquid biopsy, drug delivery, chemotherapy, autophagy, and microRNA. Additionally, research related to extracellular vesicles in breast cancer has been focused on diagnosis, treatment, and mechanisms of action of breast tumor-derived vesicles. Future studies are expected to explore the role of extracellular vesicles on autophagy and microRNA, besides investigating the application of extracellular vesicles from liquid biopsies for biomarkers and drug delivery, enabling the development and validation of therapeutic strategies for specific cancers.
Nicht nur bei traumatologischen, sondern auch bei vielen internistischen und neurologischen Notfällen ist der Schmerz das oder eines der Leitsymptome. Neben der Wiederherstellung und Sicherung der Vitalfunktionen ist die rasche und effiziente Schmerzlinderung eine der wichtigsten Aufgaben des Notarztes. Eine erfolgreiche analgetische Therapie verbessert zum einen die subjektive Befindlichkeit des Patienten und unterbricht zum anderen die durch starke Schmerzen initiierten und unterhaltenen sympathiko-adrenergen und metabolisch-endokrinen Streßreaktionen, mit all ihren nachteiligen Auswirkungen auf die Hämodynamik und Respiration. Letzteres ist eine wichtige, positive Wirkung einer guten analgetischen Therapie, insbesondere beim kranken geriatrischen Patienten, der in den Kompensationsmöglichkeiten einzelner Organsysteme oft deutlich eingeschränkt ist. Länger fortbestehende starke Schmerzen würden gerade bei diesen Patienten eine Einschränkung der Hämodynamik und Respiration perpetuieren.
Hintergrund und Fragestellung
Die Entwöhnung von Beatmungsgeräten wird nicht immer auf der primär behandelnden Intensivstation abgeschlossen. Die Weiterverlegung in andere Behandlungseinrichtungen stellt einen sensiblen Abschnitt in der Behandlung und Rehabilitation des Weaningpatienten dar. Ziel der vorliegenden Studie war die Untersuchung des Überleitungsmanagements und des Interhospitaltransfers von Weaningpatienten unter besonderer Berücksichtigung der Dokumentationsqualität.
Methodik
Es erfolge eine retrospektive Datenanalyse eines Jahrs (2018) auf 2 Intensivstationen eines Universitätsklinikums. Eingeschlossen wurden alle beatmeten Patienten mit folgenden Tracerdiagnosen: COPD, Asthma, Polytrauma, Pneumonie, Sepsis, ARDS und Reanimation (Beatmung > 24 h).
Ergebnisse
Insgesamt konnten 750 Patienten in die Untersuchung eingeschlossen werden (Alter 64 [52, 8–76; Median, IQR]; 32 % weiblich). Davon waren 48 (6,4 %) Patienten zum Zeitpunkt der Verlegung nicht entwöhnt (v. a. Sepsis und ARDS). Die Routinedokumentation war bei den Abschnitten „Spontaneous Breathing Trial“, „Bewertung der Entwöhungsbereitschaft“ und „vermutete Entwöhnbarkeit“ ausreichend, um die Erfüllung der Parameter der S2k-Leitlinie „Prolongiertes Weaning“ adäquat zu beurteilen. Vorwiegend wurden diese Patienten mit Tracheostoma (76 %) in Rehabilitationskliniken (44 %) mittels spezialisierten Rettungsmitteln des arztbegleiteten Patiententransports verlegt (75 %).
Diskussion
Die Verlegung nicht entwöhnter Patienten nach initialem Intensivaufenthalt ist ein relevantes Thema für den Interhospitaltransfer. Die Routinedokumentation eines strukturierten Weaningprozesses ist in Kernelementen ausreichend, um den Weaningprozess lückenlos zu beschreiben. Dies ist für die Kontinuität in der Weiterbehandlung dieser Patienten von großer Bedeutung.
Das Mammakarzinom ist weltweit die häufigste krebsbedingte Todesursache bei Frauen. Fortschritte in der Therapie ermöglichen zwar eine Verlängerung der Lebens- dauer, jedoch kommt es dadurch vermehrt zur Bildung von Metastasen im zentralen Nervensystem (ZNS). Die Diagnostik und Behandlung von ZNS-Metastasen sind be- grenzt und die Lebensqualität sowie Lebensdauer der Betroffenen nimmt bei zerebraler Metastasierung rapide ab. Ziel aktueller Forschungsprojekte ist daher, Biomarker zu identifizieren, die Hinweise auf eine Brustkrebserkrankung oder Metastasierung liefern. So soll eine kostengünstige, risikoarme und minimalinvasive Methode etabliert werden, die zuverlässige Daten über die Prognose und dementsprechende Therapien erbringt. Diese Arbeit hatte daher die Absicht, mithilfe von qPCR Expressionsprofile von miRNAs aus Serumproben von Brustkrebspatientinnen zu erstellen und deren Funktion als prog- nostische Biomarker für eine Metastasierung ins ZNS zu erweisen. Anhand von Metas- tasierung und Rezeptorstatus wurden die Proben in Untergruppen eingeteilt und statis- tisch mit einer gesunden Kontrollgruppe verglichen.
Insgesamt zeigte sich bei 26 miRNAs eine signifikante Dysregulation der Expression bei mindestens einer der Untergruppen. Insbesondere bei ZNS-Metastasen war das Expres- sionsmuster bei miRNA-122-5p, miRNA-296-5p, miRNA-490-3p und miRNA-576-3p sig- nifikant erhöht, während die Expression von miRNA-130a-3p, miRNA-148b-3p und miRNA-326 signifikant reduziert war. Basierend auf den Übereinstimmungen unserer Er- gebnisse mit den Daten bisheriger Forschungsprojekten wiesen vier miRNAs eine po- tenzielle Funktion als Biomarker für Metastasen auf: miRNA-122-5p, miRNA-490-3p und miRNA-130a-3p, miRNA-326. Bei ZNS-Metastasen zeigten besonders miRNA-122-5p und miRNA-490-3p statistisch relevante Veränderungen.
Um den Einfluss von miRNAs auf den gesamten Körper darzustellen, wurde mithilfe ver- schiedener Datenbanken nach entsprechenden Zielgenen und Signalwegen für die 26 identifizierten miRNAs recherchiert. Neben dem Einfluss auf Stoffwechselwege und Er- krankungen, zeigte sich bei acht Targets ein Zusammenhang mit der Entstehung von Krebs.
Ergänzend zur Identifikation von miRNA-Expressionsprofilen wurden Zellkulturversuche mit zerebralen Endothel- (cerebEND) und Brustkrebszellen (4T1) durchgeführt. Verwendet wurden zwei cerebEND- und eine 4T1-Zellreihe von Mäusen, von denen eine ce- rebEND-Kultur zuvor in der Arbeitsgruppe Burek mit einem miRNA-210-Vektor trans- fiziert wurde.
Studien belegen den Einfluss von miRNA-210 auf den mitochondrialen Stoffwechsel, Angiogenese, Reaktionen auf DNA-Schäden, Apoptose und Zellüberleben sowie auf die Proteine BRCA1, PARP1 und E-Cadherin und schreiben ihr damit eine Funktion in der Krebsentstehung und Metastasierung zu.
Zur Bestimmung der Proliferation und Aktivität der transfizierten cerebEND-210-Zellen im Verhältnis zur unbehandelten Kontrolle, wurden BrdU-Proliferationsassays und MTT- Assays mit verschiedenen Zellzahlen durchgeführt. Bei der Untersuchung der Prolifera- tion zeigte sich in beiden Versuchen eine erhöhte Aktivität der cerebEND-210-Zellen, da miRNA-210 vermutlich auch hier das Zellüberleben gesichert hat. Zudem wurde die An- heftung der Brustkrebszellen an den zerebralen Endothelzellen im Adhäsionsversuchs überprüft. Hierbei wurde eine Abnahme der Adhäsion der cerebEND-210-Zellen beo- bachtet. Vermutet wird eine Veränderung des Phänotyps der Rezeptorbindungen der cerebEND-210-Zellen.
Die Ergebnisse der Zellkulturversuche dienen als Grundlage für weitere Experimente.
Im Jahr 2017, 13 Jahre nachdem das ICMJE die prospektive Protokollregistrierung zur Notwendigkeit für zuverlässige klinische Studien erklärt hat, ist die Häufigkeit und Qualität der Studienregistrierung im Bereich der PONV-Forschung sehr gering. Für nur ein Fünftel der seit dem Jahr 2004 publizierten klinischen Studien, die in den 2020 veröffentlichten PONV Cochrane Review aufgenommen wurden, wurden Studienprotokolle registriert. Von diesen waren fast zwei Drittel retrospektiv registriert. Schlussendlich konnten weniger als 50% der prospektiv registrierten Studien als frei von Bias bei der selektiven Endpunktberichterstattung identifiziert werden. Dies ist ein alarmierendes Defizit. Diese Arbeit zeigt auch, dass registrierte Studien im Allgemeinen häufiger mit einem niedrigen Gesamtbiasrisiko beurteilt wurden. Dies legt die Studienregistrierung als Qualitätskriterium für RCTs in der klinischen PONV-Forschung nahe. Bias durch selektive Endpunktberichterstattung verringert die Vertrauenswürdigkeit von Studienergebnissen. Wissenschaftler*innen und Kliniker*innen sollten sich darüber im Klaren sein, dass nur die Adhärenz bezüglich einer adäquaten Protokollregistrierung und die transparente Berichterstattung über vordefinierte Endpunkte, unabhängig von Richtung und Bedeutung deren Ergebnisse, letztlich die Evidenz der PONV-Forschung in der Zukunft stärken kann.
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.
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.
Ziel dieser Arbeit war es, die antiinflammatorischen Effekte von Anthocyanen und Anthocyanidinen mit besonderem Augenmerk auf Delphinidin zu vergleichen. Desweiteren sollten im statistischen Vergleich Dosierungen gefunden werden, bei welchen die größte antiinflammatorische Wirksamkeit von Anthocyanen und Anthocyanidinen zu erwarten wäre und ein eventueller Unterschied in der Wirkung der verschiedenen Stoffe berechnet werden.
Die Literaturrecherche mittels der Datenbanken „Pubmed“ und „The Cochrane Library“ lieferte 24 Studien, die die Einschlusskriterien erfüllten. Für Delphinidin allein war die Datenlage zu diesem Zeitpunkt noch zu dürftig, weswegen die Suche auf die Begriffe „Anthocyanins“ in Kombination mit „Antiinflammatory Agents“ ausgedehnt wurde.
Die statistische Auswertung der Daten erfolgte unter der Fragestellung: „ Haben die Variablen Wirkstoff, Wirkdauer, Menge an Wirkstoff und Art (m-RNA oder Protein“ jeweils unter Kontrolle der anderen Variablen einen Einfluss auf die Reduktion von inflammatorischen Markern?“ Die wichtigsten Ergebnisse, die unter dieser Fragestellung errechnet werden konnten, lauten: 1. PDG zeigt eine bessere antiinflammatorische Wirksamkeit als DP und C3G, 2. Luteolin zeigt eine bessere antiinflammatorische Wirksamkeit als Cyanidin.
Gründe für eine höhere antiinflammatorische Wirksamkeit von PDG im Vergleich zu DP und C3G sind derzeit noch offen. Zu diskutieren ist unter anderem, ob DP und C3G biochemisch instabilere Komplexe sind und schneller zerfallen. Grund für eine höhere antiinflammatorische Wirksamkeit von Luteolin im Vergleich zu Cyanidin könnte eine Doppelbindung zwischen C2 und C3 sein, die bei Luteolin, nicht aber bei Cyanidin zu finden ist. In der Zusammenschau dieser Ergebnisse ist festzustellen, dass weitere Studien für eine möglichst genaue statistische Analyse nötig sind, vor allem in Bezug auf die antiinflammatorischen Effekte von Delphinidin.
The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17b- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94615.5% vs. 17.163.62%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.
Artificial intelligence (AI) is predicted to play an increasingly important role in perioperative medicine in the very near future. However, little is known about what anesthesiologists know and think about AI in this context. This is important because the successful introduction of new technologies depends on the understanding and cooperation of end users. We sought to investigate how much anesthesiologists know about AI and what they think about the introduction of AI-based technologies into the clinical setting. In order to better understand what anesthesiologists think of AI, we recruited 21 anesthesiologists from 2 university hospitals for face-to-face structured interviews. The interview transcripts were subdivided sentence-by-sentence into discrete statements, and statements were then grouped into key themes. Subsequently, a survey of closed questions based on these themes was sent to 70 anesthesiologists from 3 university hospitals for rating. In the interviews, the base level of knowledge of AI was good at 86 of 90 statements (96%), although awareness of the potential applications of AI in anesthesia was poor at only 7 of 42 statements (17%). Regarding the implementation of AI in anesthesia, statements were split roughly evenly between pros (46 of 105, 44%) and cons (59 of 105, 56%). Interviewees considered that AI could usefully be used in diverse tasks such as risk stratification, the prediction of vital sign changes, or as a treatment guide. The validity of these themes was probed in a follow-up survey of 70 anesthesiologists with a response rate of 70%, which confirmed an overall positive view of AI in this group. Anesthesiologists hold a range of opinions, both positive and negative, regarding the application of AI in their field of work. Survey-based studies do not always uncover the full breadth of nuance of opinion amongst clinicians. Engagement with specific concerns, both technical and ethical, will prove important as this technology moves from research to the clinic.
Bei 155 Ärzten und Arzthelferinnen wurde ein Notfalltraining durchgeführt. Davor und danach wurde ein multiple-choice-Test mit acht Fragen zur Reanimation durchgeführt. Es zeigte sich ein signifikanter Anstieg der richtigen Antworten von 69,7 % auf 94,7%. Teilnehmer, deren letztes Training bis zu zwei Jahre zurücklag, erreichten signifikant bessere Ergebnisse. Ebenso wurde durch Fragebögen die Ausstattung von 118 Arztpraxen untersucht. Hier zeigten sich erhebliche Unterschiede je nach Fachrichtung des Arztes. Nur ca. 20 % der Ärzte sind mit modernen AED-Geräten zur Defibrillation ausgestattet. Gerätschaften zur Intubation halten ca. 90 % vor, Sauerstoff dagegen nur ca. 80%, Sauerstoff-Reservoire weniger als die Hälfte. Opiate sind nur bei 72% bevorratet, Cordarex nur bei einem Drittel. Folgende Forderung lassen sich ableiten: -verpflichtende Fortbildungsmaßnahmen zur Reanimation -dies mindestens alle zwei Jahre (im Rahmen des Qualitätsmanagements) -Verbesserung der notfallmedizinischen Geräte- und Medikamentenausstattung
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.
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.
Es handelt sich um eine experimentelle Arbeit zur Untersuchung der Auswirkungen verschiedener Volumensubstitutionslösungen auf die Integrität der Leber in der CLP-induzierten Sepsis der Ratte. 40 Ratten wurden in 5 Grp. eingeteilt, anästhesiert und median laparotomiert. Während das Coecum der Sham-Tiere im ursprünglichen Zustand verblieb, erhielten alle anderen Tiere eine CLP. Die Tiere wurden im Anschluss entpsprechend ihrer Gruppe entweder nur mit dem Grundbedarf an NaCl (Sham) oder mit dem Grundbedarf an NaCl und dem jeweiligen Substitutionsmittel NaCl , SteroIso, Gelafundin, 6%HES 130/0,4 infundiert. Der Versuch lief über 24 h. Danach wurde die Tiere reanästhesiert, laparotomiert und eine in-vivo-Mikroskopie der Leber durchgeführt. Im Anschluss wurden sowohl hämodynamische Werte, Serumparameter und Zytokinwerte als auch histopathologische Daten ermittelt.
Background: Anemia remains one of the most common comorbidities in intensive care patients worldwide. The cause of anemia is often multifactorial and triggered by underlying disease, comorbidities, and iatrogenic factors, such as diagnostic phlebotomies. As anemia is associated with a worse outcome, especially in intensive care patients, unnecessary iatrogenic blood loss must be avoided. Therefore, this scoping review addresses the amount of blood loss during routine phlebotomies in adult (>17 years) intensive care patients and whether there are factors that need to be improved in terms of patient blood management (PBM). Methods: A systematic search of the Medline Database via PubMed was conducted according to PRISMA guidelines. The reported daily blood volume for diagnostics and other relevant information from eligible studies were charted. Results: A total of 2167 studies were identified in our search, of which 38 studies met the inclusion criteria (9 interventional studies and 29 observational studies). The majority of the studies were conducted in the US (37%) and Canada (13%). An increasing interest to reduce iatrogenic blood loss has been observed since 2015. Phlebotomized blood volume per patient per day was up to 377 mL. All interventional trials showed that the use of pediatric-sized blood collection tubes can significantly reduce the daily amount of blood drawn. Conclusion: Iatrogenic blood loss for diagnostic purposes contributes significantly to the development and exacerbation of hospital-acquired anemia. Therefore, a comprehensive PBM in intensive care is urgently needed to reduce avoidable blood loss, including blood-sparing techniques, regular advanced training, and small-volume blood collection tubes.
Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.
Balanced hydroxyethylstarch (HES 130/0.4) impairs kidney function in-vivo without inflammation
(2015)
Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6h. After 24h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1–4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion
Die Bauchlagerung von intubierten ARDS-Patient/innen mit einer schlechten Oxygenierung wird laut Leitlinie seit mehreren Jahren als supportive Therapiemaßnahme empfohlen. Im Rahmen der COVID-19 Pandemie wurde nun erstmalig die Bauchlagerung auch bei hypoxämischen, nicht-intubierten Patient/innen untersucht. Diese Fragestellung wurde in der vorliegenden Arbeit mittels einer systematischen Übersichtsarbeit betrachtet. Aufgrund der aktuellen Pandemiesituation wurden neben ARDS-Patient/innen im Allgemeinen insbesondere COVID-19 Patient/innen mit einem akuten Lungenversagen als Subgruppe untersucht.
Am 21.11.2020 wurde eine systematische Suche nach Studien in den Datenbanken MEDLINE, Cochrane COVID-19 Study Register und Living Overview of the Evidence platform durchgeführt. Die Ergebnisse wurden, wo möglich, in Form einer Meta-Analyse zusammengefasst, in Tabellen darstellt oder deskriptiv beschrieben. Das Risiko für Bias wurde jeweils für die eingeschlossenen kontrollierten Studien mittels ROBINS-I beurteilt. Die Vertrauenswürdigkeit der Evidenz der gesamten Arbeit wurde mit Hilfe des GRADE-Ansatzes untersucht.
Insgesamt wurden 30 Studien eingeschlossen, davon 4 kontrollierte Studien, keine RCTs. In 3 der kontrollierten Studien wurde die Bauchlagerung bei COVID-19 Patient/innen untersucht, in einer bei Patient/innen mit einem anderweitig verursachten ARDS. Es ist unklar, ob die Bauchlagerung die Intubationsrate (RR = 0,92; 95% KI: 0,59 - 1,44; I² = 65%; sehr niedrige Vertrauenswürdigkeit der Evidenz), die Mortalität (RR = 0,55; 95% KI: 0,23 - 1,30; I² = 60%; sehr niedrige Vertrauenswürdigkeit der Evidenz) und die Wahrscheinlichkeit für eine Aufnahme auf die Intensivstation (RR = 0,94; 95% KI: 0,54 - 1,63; I2 = 71%; sehr niedrige Vertrauenswürdigkeit der Evidenz) verringern kann. Auch für die anderen betrachteten Endpunkte konnte kein signifikanter Effekt der Bauchlagerung nachgewiesen werden Im Vergleich der Subgruppen „Nicht-COVID-19“ (8 Studien) und „COVID-19“ (22 Studien) konnten in Bezug auf alle betrachteten Endpunkte keine relevanten Unterschiede festgestellt werden.
Insgesamt ist die Evidenz nicht ausreichend, um Vor- und Nachteile der Bauchlagerung für nicht-intubierte ARDS Patient/innen gegenüber der üblichen Rückenlagerung aufzuzeigen und diese für die Praxis zu empfehlen.
Background
The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS).
Methods
This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay.
Results
Most patients (91%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100% of the cases, oropharyngeal swabs only in 77%. Blood samples were positive in 26% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009).
Conclusions
COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.
In this study, the ability of a multiwalled carbon nanotube functionalized with fluorescein isothiocyanate (MWCNT-FITC) was assessed as a prospective central nervous system-targeting drug delivery system to permeate the blood-brain barrier. The results indicated that the MWCNT-FITC conjugate is able to penetrate microvascular cerebral endothelial monolayers; its concentrations in the Transwell® system were fully equilibrated after 48 hours. Cell viability test, together with phase-contrast and fluorescence microscopies, did not detect any signs of MWCNT-FITC toxicity on the cerebral endothelial cells. These microscopic techniques also revealed presumably the intracellular localization of fluorescent MWCNT-FITCs apart from their massive nonfluorescent accumulation on the cellular surface due to nanotube lipophilic properties. In addition, the 1,000 ps molecular dynamics simulation in vacuo discovered the phenomenon of carbon nanotube aggregation driven by van der Waals forces via MWCN-TFITC rapid dissociation as an intermediate phase.
Background: The adequate choice of perioperative antibiotic prophylaxis (PAP) could influence the risk of surgical site infections (SSIs) in general surgery. A new local PAP guideline was implemented in May 2017 and set the first-generation cefazolin (CFZ) instead the second-generation cefuroxime (CXM) as the new standard prophylactic antibiotic. The aim of this study was to compare the risk of SSIs after this implementation in intra-abdominal infections (IAIs) without sepsis. Methods: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Germany analyzing patients after emergency surgery during 2016 to 2019 (n = 985), of which patients receiving CXM or CFZ were selected (n = 587). Propensity score matching was performed to ensure a comparable risk of SSIs in both groups. None-inferiority margin for SSIs was defined as 8% vs. 4%. Results: Two matched cohorts with respectively 196 patients were compared. The rate of SSIs was higher in the CFZ group (7.1% vs. 3.6%, p = 0.117) below the non-inferiority margin. The rate of other postoperative infections was significantly higher in the CFZ group (2.0% vs. 8.7%, p = 0.004). No other differences including postoperative morbidity, mortality or length-of-stay were observed. Conclusion: Perioperative antibiotic prophylaxis might be safely maintained by CFZ even in the treatment of intra-abdominal infections.
In my thesis, I characterized aGPCRs Adgrl1 and Adgrl3, tight junction proteins and the blood-DRG-barrier in rats’ lumbar dorsal root ganglions after traumatic neuropathy. In contrast to the otherwise tightly sealed barriers shielding neural tissues, the dorsal root ganglion’s neuron rich region is highly permeable in its healthy state. Furthermore, the DRG is a source of ectopic signal generation during neuropathy; the exact origin of which is still unclear. I documented expression of Adgrl1 and Adgrl3 in NF200 + , CGRP + and IB4 + neurons. One week after CCI, I observed transient downregulation of Adgrl1 in non-peptidergic nociceptors (IB4+). In the context of previous data, dCirl deletion causing an allodynia-like state in Drosophila, our research hints to a possible role of Adgrl1 nociceptive signal processing and pain resolution in neuropathy. Furthermore, I demonstrated similar claudin-1, claudin-12, claudin-19, and ZO-1 expression of the dorsal root ganglion’s neuron rich and fibre rich region. Claudin-5 expression in vessels of the neuron rich region was lower compared to the fibre rich region. Claudin-5 expression was decreased one week after nerve injury in vessels of the neuron rich region while permeability for small and large injected molecules remained unchanged. Nevertheless, we detected more CD68+ cells in the neuron rich region one week after CCI. As clinically relevant conclusion, we verified the high permeability of the neuron rich regions barrier as well as a vessel specific claudin-5 downregulation after CCI. We observed increased macrophage invasion into the neuron rich region after CCI. Furthermore, we identified aGPCR as potential target for further research and possible treatments for neuropathy, which should be easily accessible due to the blood-DRG-barriers leaky nature. Its precise function in peripheral tissues, its mechanisms of activation, and its role in pain resolution should be evaluated further.
Die wichtigsten Barrieren des peripheren Nerven sind die Myelin-Barriere und die Blut-Nerven-Schranke. Sie übernehmen eine bedeutende Aufgabe beim Schutz des Nerven vor externen Einflüssen, dem Bewahren der nervalen Homöostase und der Aufrechterhaltung der Nervenleitungsgeschwindigkeit. Eine Öffnung der peripheren Barriere wird oft mit neuropathischen Schmerzen assoziiert. Im Rahmen dieser Dissertation habe ich mittels Immunfluoreszenzfärbung, Permeabilitätstest, Western Blot und Polymerase-Kettenreaktion die Barrierefunktion des peripheren Nervensystems bei weiblichen Cldn12-KO Mäusen untersucht. Sowohl bei den WT Mäusen als auch bei den Cldn12-KO Mäusen konnte eine intakte Barrierefunktion des peripheren Nerven nachgewiesen werden.
Propofol is a widely used general anesthetic in clinical practice, but its use is limited by its water-insoluble nature and associated pharmacokinetic and pharmacodynamic limitations. Therefore, researchers have been searching for alternative formulations to lipid emulsion to address the remaining side effects. In this study, novel formulations for propofol and its sodium salt Na-propofolat were designed and tested using the amphiphilic cyclodextrin (CD) derivative hydroxypropyl-β-cyclodextrin (HPβCD). The study found that spectroscopic and calorimetric measurements suggested complex formation between propofol/Na-propofolate and HPβCD, which was confirmed by the absence of an evaporation peak and different glass transition temperatures. Moreover, the formulated compounds showed no cytotoxicity and genotoxicity compared to the reference. The molecular modeling simulations based on molecular docking predicted a higher affinity for propofol/HPβCD than for Na-propofolate/HPβCD, as the former complex was more stable. This finding was further confirmed by high-performance liquid chromatography. In conclusion, the CD-based formulations of propofol and its sodium salt may be a promising option and a plausible alternative to conventional lipid emulsions.
Trotz des breiten, klinischen Einsatzes des Propofols haben sich aufgrund bestehender Nebenwirkungen zunehmend Bestrebung entwickelt, alternative Formulierungen zur Lipidemulsion zu finden. In dieser Arbeit wurden die Substanzen Propofol/HPβCD und Na-Propofolat/HPβCD als alternative Formulierungen des Propofols mittels 1H-NMR-Spektroskopie, molekularer Modellierungen, DSC-Messungen, Zytotoxizitätstests (MTT-Test, LDH-Assay, EZ4U-Test) und dem Comet-Assay als Genotoxizitätstest auf biologische, chemische und physikalische Eigenschaften untersucht. Die Frage nach der Komplexbildung zwischen Propofol und HPβCD lässt sich nicht allein auf Basis des 1D-1H-NMR-Spektrums beantworten. Allerdings lässt sich mit Hilfe der 1H-NMR-Spektroskopie für Na-Propofolat/HPβCD das Vorliegen als deprotonierte Form nachweisen. Anderseits legen aber die DSC-Messungen eine Komplexbildung zwischen Propofol und HPβCD nahe. Zum einen ergibt sich das aus den unterschiedlichen Glasübergangstemperaturen der Substanzen. Zum anderen zeigt der Kurvenverlauf für HPβCD als auch für Na-Propofolat/HPβCD und Propofol/HPβCD keinen Verdampfungspeak bis zu der untersuchten maximalen Temperatur von 280 °C trotz des Propofol-Siedepunktes von 256 °C. Die molekularen Modellierungen legen nahe, dass die Bindung zwischen Propofol und Cyclodextrin über die Isopropylgruppen des Propofols erfolgt, wobei der aromatische Ring nicht in die Cavität des Cyclodextrinringes eindringt. Aus den molekularen Modellierungen ergeben sich Enthalpiewerte, die in ihrer Größenordnung schwachen Wasserstoffbrückenbindungen entsprechen. Für das Na-Propofolat/HPβCD lässt sich eine leichtere Abspaltung des Propofols aus dem Komplex voraussagen, wohingegen für Propofol/HPβCD die Abspaltung langsamer, aber über einen längeren Zeitraum erfolgen dürfte. Im Vergleich zu der hohen Zytotoxizität des Propofols als Lipidemulsion ergibt sich aus den an der CerebEND-Zelllinie durchgeführten Zyotoxizitätstests für HPβCD, Propofol/HPβCD und Na-Propofolat/HPβCD kein Nachweis einer Zytotoxizität nach 24-stündiger Exposition. Die Resultate zeigen für die drei Testverfahren die jeweils gleiche Reihenfolge mit der höchsten Zellvitalität für die mit Na-Propofolat/HPβCD behandelten Zellen und der niedrigsten Zellvitalität für HPβCD. In dem Comet-Assay zeigt sich nach 24-stündiger Exposition bei 37 °C für HPβCD, Propofol/HPβCD und Na-Propofolat/HPβCD keine genotoxische Wirkung an der HL-60-Zelllinie. Die Ergebnisse dieser Arbeit sprechen für die Fortsetzung der Untersuchungen von Propofol/HPβCD und Na-Propofolat/HPβCD als aussichtsreiche Option der Propofol-Formulierungen.
Hintergrund
Internationale Studien belegen negative Auswirkungen der COVID-19-Pandemie auf Stimmung und Stresslevel befragter Personen. Auch konnten Zusammenhänge zwischen der Pandemie und höheren Schmerzstärken sowie stärkerer schmerzbedingter Beeinträchtigung nachgewiesen werden. Die Studienlage dazu, ob ältere Menschen besser oder schlechter mit der Pandemie und ihren Auswirkungen umgehen können als jüngere Personen, ist aber uneindeutig.
Methodik
Seit einigen Jahren bietet das Universitätsklinikum Würzburg ein multimodales Schmerztherapieprogramm für SeniorInnen an. Für die vorliegende Arbeit wurden retrospektiv klinische Routinedaten zum Zeitpunkt des interdisziplinären multimodalen Assessments von n = 75 TeilnehmerInnen in den Jahren 2018 und 2019 mit denen von n = 42 Patientinnen während der COVID-19-Pandemie 2020–2021 verglichen. Wir untersuchten Schmerz, psychische Belastung und körperliches Funktionsniveau mithilfe des Deutschen Schmerzfragebogens, klinischer Diagnostik und geriatrischer Funktionstests.
Ergebnisse
Die beiden Teilstichproben unterschieden sich nicht in demografischen Merkmalen. Bezüglich Schmerzintensität und Beeinträchtigung sowie der psychischen Belastung fanden sich ebenfalls keine signifikanten Unterschiede. Lediglich die Anzahl der schmerzbedingt beeinträchtigten Tage war vor Corona signifikant höher. Die geriatrischen Funktionstests zeigten signifikant bessere Werte während der Pandemie an.
Diskussion
Die vorliegenden Daten zeigen keine Verschlechterung von Schmerz und körperlichem sowie psychischem Wohlbefinden bei SeniorInnen vor dem Hintergrund der Pandemie. Weitere Studien sollten die möglichen Gründe dafür untersuchen. Diese könnten in einer höheren Resilienz der SeniorInnen basierend auf ihrer Lebenserfahrung, finanziellen Sicherheit oder einer geringeren Veränderung des Lebensalltags liegen.
Background:
Studies have reported on the incidence of sedation-related adverse events (AEs), but little is known about their impact on health care costs and resource use.
Methods: Health care providers and payers in five countries were recruited for an online survey by independent administrators to ensure that investigators and respondents were blinded to each other. Surveys were conducted in the local language and began with a "screener" to ensure that respondents had relevant expertise and experience. Responses were analyzed using Excel and R, with the Dixon's Q statistic used to identify and remove outliers. Global and country-specific average treatment patterns were calculated via bootstrapping; costs were mean values. The sum product of costs and intervention probability gave a cost per AE.
Results: Responses were received from 101 providers and 26 payers, the majority having. 5 years of experience. At a minimum, the respondents performed a total of 3,430 procedural sedations per month. All AEs detailed occurred in clinical practice in the last year and were reported to cause procedural delays and cancellations in some patients. Standard procedural sedation costs ranged from (sic)74 (Germany) to $2,300 (US). Respondents estimated that AEs would increase costs by between 16% (Italy) and 179% (US). Hypotension was reported as the most commonly observed AE with an associated global mean cost (interquartile range) of $43 ($27-$68). Other frequent AEs, including mild hypotension, bradycardia, tachycardia, mild oxygen desaturation, hypertension, and brief apnea, were estimated to increase health care spending on procedural sedation by $2.2 billion annually in the US.
Conclusion: All sedation-related AEs can increase health care costs and result in substantial delays or cancellations of subsequent procedures. The prevention of even minor AEs during procedural sedation may be crucial to ensuring its value as a health care service.
The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = −0.495), PCT (r\(_s\) = −0.413), IL-6 (r\(_s\) = −0.429), IL-1β (r\(_s\) = −0.440) and IL-10 (r\(_s\) = −0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.
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.
Background
Data on the routine use of video-assisted laryngoscopy in peri-operative intubations are rather inconsistent and ambiguous, in part due to small populations and non-uniform outcome measures in past trials. Failed or prolonged intubation procedures are a reason for relevant morbidity and mortality. This study aims to determine whether video-assisted laryngoscopy (with both Macintosh-shaped and hyperangulated blades) is at least equal to the standard method of direct laryngoscopy with respect to the first-pass success rate. Furthermore, validated tools from the field of human factors will be applied to examine within-team communication and task load during this critical medical procedure.
Methods
In this randomized, controlled, three-armed parallel group design, multi-centre trial, a total of more than 2500 adult patients scheduled for perioperative endotracheal intubation will be randomized. In equally large arms, video-assisted laryngoscopy with a Macintosh-shaped or a hyperangulated blade will be compared to the standard of care (direct laryngoscopy with Macintosh blade). In a pre-defined hierarchical analysis, we will test the primary outcome for non-inferiority first. If this goal should be met, the design and projected statistical power also allow for subsequent testing for superiority of one of the interventions.
Various secondary outcomes will account for patient safety considerations as well as human factors interactions within the provider team and will allow for further exploratory data analysis and hypothesis generation.
Discussion
This randomized controlled trial will provide a solid base of data in a field where reliable evidence is of major clinical importance. With thousands of endotracheal intubations performed every day in operating rooms around the world, every bit of performance improvement translates into increased patient safety and comfort and may eventually prevent significant burden of disease. Therefore, we feel confident that a large trial has the potential to considerably benefit patients and anaesthetists alike.
Trial registration
ClincalTrials.gov NCT05228288.
Protocol version
1.1, November 15, 2021.
Physical and mental well-being during the COVID-19 pandemic is typically assessed via surveys, which might make it difficult to conduct longitudinal studies and might lead to data suffering from recall bias. Ecological momentary assessment (EMA) driven smartphone apps can help alleviate such issues, allowing for in situ recordings. Implementing such an app is not trivial, necessitates strict regulatory and legal requirements, and requires short development cycles to appropriately react to abrupt changes in the pandemic. Based on an existing app framework, we developed Corona Health, an app that serves as a platform for deploying questionnaire-based studies in combination with recordings of mobile sensors. In this paper, we present the technical details of Corona Health and provide first insights into the collected data. Through collaborative efforts from experts from public health, medicine, psychology, and computer science, we released Corona Health publicly on Google Play and the Apple App Store (in July 2020) in eight languages and attracted 7290 installations so far. Currently, five studies related to physical and mental well-being are deployed and 17,241 questionnaires have been filled out. Corona Health proves to be a viable tool for conducting research related to the COVID-19 pandemic and can serve as a blueprint for future EMA-based studies. The data we collected will substantially improve our knowledge on mental and physical health states, traits and trajectories as well as its risk and protective factors over the course of the COVID-19 pandemic and its diverse prevention measures.
Hintergrund
Im Rahmen der Pandemie des SARS-CoV-2-Virus erlangte das Patientenkollektiv der Schwangeren früh Aufmerksamkeit. Initial wurde angesichts sich früh abzeichnender Krankheitsfälle bei jüngeren Patienten mit einem erheblichen Aufkommen peripartal zu betreuender, COVID-19-positiver Schwangerer gerechnet.
Ziel der Arbeit
Diese Arbeit vermittelt einen Einblick in die SARS-CoV-2-Infektionszahlen im Rahmen der geburtshilflichen Anästhesie zu Beginn der Pandemie sowie während der zweiten Infektionswelle in Deutschland.
Methoden
Über das COALA-Register (COVID-19 related Obstetric Anaesthesia Longitudinal Assessment-Registry) wurden sowohl von März bis Mai 2020 als auch von Oktober 2020 bis Februar 2021 in Deutschland und der Schweiz wöchentlich prospektiv Daten zu Verdachts- und bestätigten SARS-CoV-2-Fällen bei Schwangeren zum Zeitpunkt der Geburt erhoben. Betrachtet wurden die Verteilung dieser auf die Anzahl der Geburten, Zentren und Erhebungswochen sowie mütterliche Charakteristika und Krankheitsverläufe.
Ergebnisse
Neun Zentren haben im Verlauf 44 SARS-CoV-2-positive Schwangere zum Zeitpunkt der Geburt bei 7167 Geburten (0,6 %) gemeldet (3 Fälle auf 2270 Geburten (0,4 %) und 41 Fälle auf 4897 Geburten (0,8 %)). Berichtet wurden 2 schwere COVID-19-Verläufe (n = 1 mit Todesfolge nach ECMO, n = 1 mit ECMO überlebt). Bei 28 (68 %) Patientinnen verlief die Infektion asymptomatisch. Ein Neugeborenes wurde im Verlauf positiv auf SARS-CoV‑2 getestet.
Schlussfolgerung
Mithilfe des Registers konnte das Auftreten von Fällen zu Beginn der Pandemie zeitnah eingeschätzt werden. Es traten sporadisch Verdachtsfälle bzw. bestätigte Fälle auf. Aufgrund fehlender flächendeckender Testung muss aber von einer Dunkelziffer asymptomatischer Fälle ausgegangen werden. Während der zweiten Infektionswelle wurden 68 % asymptomatische Fälle gemeldet. Jedoch kann es bei jungen, gesunden Patientinnen ohne das Vorliegen typischer Risikofaktoren zu schwerwiegenden Verläufen kommen.
Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS).
Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included.
Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay.
Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.
Backround: In February 2021, the first formal evidence and consensus-based (S3) guidelines for the inpatient treatment of patients with COVID-19 were published in Germany and have been updated twice during 2021. The aim of the present study is to re-evaluate the dissemination pathways and strategies for ICU staff (first evaluation in December 2020 when previous versions of consensus-based guidelines (S2k) were published) and question selected aspects of guideline adherence of standard care for patients with COVID-19 in the ICU. Methods: We conducted an anonymous online survey among German intensive care staff from 11 October 2021 to 11 November 2021. We distributed the survey via e-mail in intensive care facilities and requested redirection to additional intensive care staff (snowball sampling). Results: There was a difference between the professional groups in the number, selection and qualitative assessment of information sources about COVID-19. Standard operating procedures were most frequently used by all occupational groups and received a high quality rating. Physicians preferred sources for active information search (e.g., medical journals), while nurses predominantly used passive consumable sources (e.g., every-day media). Despite differences in usage behaviour, the sources were rated similarly in terms of the quality of the information on COVID-19. The trusted organizations have not changed over time. The use of guidelines was frequently stated and highly recommended. The majority of the participants reported guideline-compliant treatment. Nevertheless, there were certain variations in the use of medication as well as the criteria chosen for discontinuing non-invasive ventilation (NIV) compared to guideline recommendations. Conclusions: An adequate external source of information for nursing staff is lacking, the usual sources of physicians are only appropriate for the minority of nursing staff. The self-reported use of guidelines is high.
Vaccination hesitancy is a threat to herd immunity. Healthcare workers (HCWs) play a key role in promoting Coronavirus disease 2019 (COVID-19) vaccination in the general population. We therefore aimed to provide data on COVID-19 vaccination acceptance/hesitancy among German HCWs. For this exploratory, cross-sectional study, an online survey was conducted in February 2021. The survey included 54 items on demographics; previous vaccination behavior; trust in vaccines, physicians, the pharmaceutical industry and health politics; fear of adverse effects; assumptions regarding the consequences of COVID-19; knowledge about vaccines; and information seeking behavior. Odds ratios with 95% confidence intervals were calculated and chi-square tests were performed. Four thousand five hundred surveys were analyzed. The overall vaccination acceptance was 91.7%. The age group ≤20 years showed the lowest vaccination acceptance. Factors associated with vaccination hesitancy were lack of trust in authorities and pharmaceutical companies. Attitudes among acquaintances were associated with vaccination hesitancy too. Participants with vaccination hesitancy more often obtained information about COVID-19 vaccines via messenger services or online video platforms and underperformed in the knowledge test. We found high acceptance amongst German HCWs. Several factors associated with vaccination hesitancy were identified which could be targeted in HCW vaccination campaigns.
(1) Background: Health care workers (HCWs) play a key role in increasing anti-COVID vaccination rates. Fear of potential side effects is one of the main reasons for vaccine hesitancy. We investigated which side effects are of concern to HCWs and how these are associated with vaccine hesitancy. (2) Methods: Data were collected in an online survey in February 2021 among HCWs from across Germany with 4500 included participants. Free-text comments on previously experienced vaccination side effects, and fear of short- and long-term side effects of the COVID-19 vaccination were categorized and analyzed. (3) Results: Most feared short-term side effects were vaccination reactions, allergic reactions, and limitations in daily life. Most feared long-term side effects were (auto-) immune reactions, neurological side effects, and currently unknown long-term consequences. Concerns about serious vaccination side effects were associated with vaccination refusal. There was a clear association between refusal of COVID-19 vaccination in one's personal environment and fear of side effects. (4) Conclusions: Transparent information about vaccine side effects is needed, especially for HCW. Especially when the participants' acquaintances advised against vaccination, they were significantly more likely to fear side effects. Thus, further education of HCW is necessary to achieve good information transfer in clusters as well.
CXCL10 Controls Inflammatory Pain via Opioid Peptide- Containing Macrophages in Electroacupuncture
(2014)
Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture.
We present an exceptional case of recurrent cycling‐induced spontaneous pneumomediastinum and pneumopericardium in a female patient without any trauma. Radiological and endoscopic examinations were carried out to exclude other differential diagnoses. Decision for in‐hospital observation and conservative treatment was made. No symptoms were reported 12 months after return to sports activity.
Cyclodextrins (CDs) are cyclic oligosaccharide structures that could be used for theranostic applications in personalized medicine. These compounds have been widely utilized not only for enhancing drug solubility, stability, and bioavailability but also for controlled and targeted delivery of small molecules. These compounds can be complexed with various biomolecules, such as peptides or proteins, via host-guest interactions. CDs are amphiphilic compounds with water-hating holes and water-absorbing surfaces. Architectures of CDs allow the drawing and preparation of CD-based polymers (CDbPs) with optimal pharmacokinetic and pharmacodynamic properties. These polymers can be cloaked with protein corona consisting of adsorbed plasma or extracellular proteins to improve nanoparticle biodistribution and half-life. Besides, CDs have become famous in applications ranging from biomedicine to environmental sciences. In this review, we emphasize ongoing research in biomedical fields using CD-based centered, pendant, and terminated polymers and their interactions with protein corona for theranostic applications. Overall, a perusal of information concerning this novel approach in biomedicine will help to implement this methodology based on host-guest interaction to improve therapeutic and diagnostic strategies.
Background
High doses of capsaicin are recommended for the treatment of neuropathic pain. However, low doses evoke mechanical hypersensitivity. Activation of the capsaicin chemosensor transient receptor potential vanilloid 1 (TRPV1) induces neurogenic inflammation. In addition to the release of pro-inflammatory mediators, reactive oxygen species are produced. These highly reactive molecules generate oxidised phospholipids and 4-hydroxynonenal (4-HNE) which then directly activate TRP ankyrin 1 (TRPA1). The apolipoprotein A-I mimetic peptide D-4F neutralises oxidised phospholipids. Here, we asked whether D-4F ameliorates neurogenic hypersensitivity in rodents by targeting reactive oxygen species and 4-HNE in the capsaicin-evoked pain model.
Results
Co-application of D-4F ameliorated capsaicin-induced mechanical hypersensitivity and allodynia as well as persistent heat hypersensitivity measured by Randell–Selitto, von Frey and Hargreaves test, respectively. In addition, mechanical hypersensitivity was blocked after co-injection of D-4F with the reactive oxygen species analogue H2O2 or 4-HNE. In vitro studies on dorsal root ganglion neurons and stably transfected cell lines revealed a TRPA1-dependent inhibition of the calcium influx when agonists were pre-incubated with D-4F. The capsaicin-induced calcium influx in TRPV1-expressing cell lines and dorsal root ganglion neurons sustained in the presence of D-4F.
Conclusions
D-4F is a promising compound to ameliorate TRPA1-dependent hypersensitivity during neurogenic inflammation.
Inflammation of the central nervous system (CNS) is associated with diseases such as multiple sclerosis, stroke and neurodegenerative diseases. Compromised integrity of the blood-brain barrier (BBB) and increased migration of immune cells into the CNS are the main characteristics of brain inflammation. Clustered protocadherins (Pcdhs) belong to a large family of cadherin-related molecules. Pcdhs are highly expressed in the CNS in neurons, astrocytes, pericytes and epithelial cells of the choroid plexus and, as we have recently demonstrated, in brain microvascular endothelial cells (BMECs). Knockout of a member of the Pcdh subfamily, PcdhgC3, resulted in significant changes in the barrier integrity of BMECs. Here we characterized the endothelial PcdhgC3 knockout (KO) cells using paracellular permeability measurements, proliferation assay, wound healing assay, inhibition of signaling pathways, oxygen/glucose deprivation (OGD) and a pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) treatment. PcdhgC3 KO showed an increased paracellular permeability, a faster proliferation rate, an altered expression of efflux pumps, transporters, cellular receptors, signaling and inflammatory molecules. Serum starvation led to significantly higher phosphorylation of extracellular signal-regulated kinases (Erk) in KO cells, while no changes in phosphorylated Akt kinase levels were found. PcdhgC3 KO cells migrated faster in the wound healing assay and this migration was significantly inhibited by respective inhibitors of the MAPK-, β-catenin/Wnt-, mTOR- signaling pathways (SL327, XAV939, or Torin 2). PcdhgC3 KO cells responded stronger to OGD and TNFα by significantly higher induction of interleukin 6 mRNA than wild type cells. These results suggest that PcdhgC3 is involved in the regulation of major signaling pathways and the inflammatory response of BMECs.
Die Maligne Hyperthermie (MH) ist eine metabolische Myopathie. Sie veranlagt zu einer potentiell lebensgefährlichen Stoffwechselentgleisung, die durch Exposition mit bestimmten Triggersubstanzen, insbesondere volatilen Anästhetika und depolarisierenden Muskelrelaxantien, ausgelöst wird. Dabei führt ein Defekt in der Membran des sarkoplasmatischen Retikulums der Skelettmuskulatur zur unkontrollierten Stoffwechselsteigerung. Zahlreiche Medikamente weisen in ihrem Nebenwirkungsprofil das Risiko von Rhabdomyolysen oder Myalgien auf. Unter Therapie von Cerivastatin kam es in 52 Fällen zu tödlichen Verläufen, so dass das Medikament 2001 vom Markt genommen wurde. Wir untersuchten Maligne Hyperthermie suszeptible Schweinemuskeln im In-vitro-Kontrakturtest (IVCT) unter Inkubation mit Atorvastatin, Simvastatin, Levofloxacin, Ciprofloxacin und Gemfibrozil. Für diese Medikamente sind derartige unerwünschte Arzneimittelwirkungen beschrieben. Wir konnten dabei zeigen, dass der Maligne Hyperthermie suszeptible (MHS) Muskel anscheinend empfindlicher auf Atorvastatin, Simvastatin, Levofloxacin und Ciprofloxacin reagiert als der Maligne Hyperthermie negative (MHN). Das zeigte sich anhand der gegenüber den nicht suszeptiblen Muskeln signifikant höher ansteigenden Ruhespannung der MHS-Muskelpräparate im IVCT. Wir erklären dieses Ergebnis durch die beim MHS-Muskel labilere Ca2+-Homöostase. Gemfibrozil scheint hingegen auf die Ca2+-Homöostase keinen Einfluss zu haben, jedoch in hohen Konzentrationen myotoxisch zu wirken. Eine Kombination mit anderen Medikamenten, die durch die gleichen Enzymsysteme abgebaut werden, sollte daher nur mit Vorsicht erfolgen, um eine Kumulation im Organismus zu vermeiden.