Author: "Ulrich Goebel" - Searchworks@Jio Institute Digital Library Search Results

177 results on '"Ulrich Goebel"'

1. Perioperative point-of-care-testing of plasmacholinesterases identifies older patients at risk for postoperative delirium: an observational prospective cohort study

Author: Matthias S. Gruendel, Wibke Brenneisen, Jakob Wollborn, Gerrit Haaker, Melanie Meersch, Simone Gurlit, and Ulrich Goebel
Subjects: Cholinesterases, Orthopaedics, Traumatology, Delirium, Geriatrics, RC952-954.6
Abstract: Abstract Background Postoperative delirium (POD) is a severe perioperative complication that may increase mortality and length-of-stay in older patients. Moreover, POD is a major economic burden to any healthcare system. An altered expression of Acetylcholine- and Butyrylcholinesterases (AChE, BuChE) due to an unbalanced neuroinflammatory response to trauma or an operative stimulus has been reported to play an essential role in the development of POD. We investigated if perioperative measurement of cholinesterases (ChEs) can help identifying patients at risk for the occurrence of POD in both, scheduled and emergency surgery patients. Methods This monocentric prospective observational cohort study was performed in a tertiary hospital (departments of orthopaedic surgery and traumatology). One hundred and fifty-one patients aged above 75 years were enrolled for scheduled (n = 76) or trauma-related surgery (n = 75). Exclusion criteria were diagnosed dementia and anticholinergic medication. Plasma samples taken pre- and postoperatively were analysed regarding AChE and BuChE activity. Furthermore, perioperative assessment using different cognitive tests was performed. The type of anaesthesia (general vs. spinal anaesthesia) was analysed. Primary outcome was the incidence of POD assessed by the approved Confusion Assessment Method (CAM) in combination with the expression of AChE and BuChE. Results Of 151 patients included, 38 (25.2%) suffered from POD; 11 (14%) in scheduled and 27 (36%) in emergency patients. AChE levels showed no difference throughout groups or time course. Trauma patients had lower BuChE levels prior to surgery than scheduled patients (p
Published: 2024
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2. Capillary leak and endothelial permeability in critically ill patients: a current overview

Author: Babak Saravi, Ulrich Goebel, Lars O. Hassenzahl, Christian Jung, Sascha David, Aarne Feldheiser, Matthias Stopfkuchen-Evans, and Jakob Wollborn
Subjects: Capillary leak syndrome, Critical care, Fluid balance, Endothelial permeability, Angiopoietin-2, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Capillary leak syndrome (CLS) represents a phenotype of increased fluid extravasation, resulting in intravascular hypovolemia, extravascular edema formation and ultimately hypoperfusion. While endothelial permeability is an evolutionary preserved physiological process needed to sustain life, excessive fluid leak—often caused by systemic inflammation—can have detrimental effects on patients’ outcomes. This article delves into the current understanding of CLS pathophysiology, diagnosis and potential treatments. Systemic inflammation leading to a compromise of endothelial cell interactions through various signaling cues (e.g., the angiopoietin–Tie2 pathway), and shedding of the glycocalyx collectively contribute to the manifestation of CLS. Capillary permeability subsequently leads to the seepage of protein-rich fluid into the interstitial space. Recent insights into the importance of the sub-glycocalyx space and preserving lymphatic flow are highlighted for an in-depth understanding. While no established diagnostic criteria exist and CLS is frequently diagnosed by clinical characteristics only, we highlight more objective serological and (non)-invasive measurements that hint towards a CLS phenotype. While currently available treatment options are limited, we further review understanding of fluid resuscitation and experimental approaches to target endothelial permeability. Despite the improved understanding of CLS pathophysiology, efforts are needed to develop uniform diagnostic criteria, associate clinical consequences to these criteria, and delineate treatment options. Graphical Abstract
Published: 2023
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3. Angiopoietin-2 is associated with capillary leak and predicts complications after cardiac surgery

Author: Jakob Wollborn, Zilu Zhang, Julie Gaa, Moritz Gentner, Christian Hausmann, Felix Saenger, Karina Weise, Samuel Justice, Jean-Luca Funk, Hans Felix Staehle, Marie Thomas, Raphael R. Bruno, Babak Saravi, Jan O. Friess, Markus Marx, Hartmut Buerkle, Georg Trummer, Jochen D. Muehlschlegel, Daniel Reker, Ulrich Goebel, and Felix Ulbrich
Subjects: Cardiac surgery, Capillary leak syndrome, Critical care, Fluid balance, Endothelial permeability, Angiopoietin-2, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. We hypothesized that markers of endothelial injury and inflammation are associated with capillary leak, ultimately increasing the risk of postoperative complications. Methods In this prospective, observational, multidisciplinary cohort study at our tertiary academic medical center, we recruited 405 cardiac surgery patients. Patients were assessed daily using body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of serum biomarkers. Multivariable models, as well as machine learning, were used to study the association of angiopoietin-2 with extracellular water as well as common complications after cardiac surgery. Results The majority of patients underwent coronary artery bypass grafting, valvular, or aortic surgeries. Across the groups, extracellular water increased postoperatively (20 ± 6 preoperatively to 29 ± 7L on postoperative day 2; P
Published: 2023
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4. Argon preconditioning protects neuronal cells with a Toll-like receptor-mediated effect

Author: Stefanie Scheid, Adrien Lejarre, Jakob Wollborn, Hartmut Buerkle, Ulrich Goebel, and Felix Ulbrich
Subjects: apoptosis, inflammation, interleukin-8, neuroprotection, rotenone, sh-sy5y, toll-like receptor 2, toll-like receptor 4, Neurology. Diseases of the nervous system, RC346-429
Abstract: The noble gas argon has the potential to protect neuronal cells from cell death. So far, this effect has been studied in treatment after acute damage. Preconditioning using argon has not yet been investigated. In this study, human neuroblastoma SH-SY5Y cells were treated with different concentrations of argon (25%, 50%, and 74%; 21% O2, 5% CO2, balance nitrogen) at different time intervals before inflicting damage with rotenone (20 µM, 4 hours). Apoptosis was determined by flow cytometry after annexin V and propidium iodide staining. Surface expressions of Toll-like receptors 2 and 4 were also examined. Cells were also processed for analysis by western blot and qPCR to determine the expression of apoptotic and inflammatory proteins, such as extracellular-signal regulated kinase (ERK1/2), nuclear transcription factor-κB (NF-κB), protein kinase B (Akt), caspase-3, Bax, Bcl-2, interleukin-8, and heat shock proteins. Immunohistochemical staining was performed for TLR2 and 4 and interleukin-8. Cells were also pretreated with OxPAPC, an antagonist of TLR2 and 4 to elucidate the molecular mechanism. Results showed that argon preconditioning before rotenone application caused a dose-dependent but not a time-dependent reduction in the number of apoptotic cells. Preconditioning with 74% argon for 2 hours was used for further experiments showing the most promising results. Argon decreased the surface expression of TLR2 and 4, whereas OxPAPC treatment partially abolished the protective effect of argon. Argon increased phosphorylation of ERK1/2 but decreased NF-κB and Akt. Preconditioning inhibited mitochondrial apoptosis and the heat shock response. Argon also suppressed the expression of the pro-inflammatory cytokine interleukin-8. Immunohistochemistry confirmed the alteration of TLRs and interleukin-8. OxPAPC reversed the argon effect on ERK1/2, Bax, Bcl-2, caspase-3, and interleukin-8 expression, but not on NF-κB and the heat shock proteins. Taken together, argon preconditioning protects against apoptosis of neuronal cells and mediates its action via Toll-like receptors. Argon may represent a promising therapeutic alternative in various clinical settings, such as the treatment of stroke.
Published: 2023
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5. Neuroprotection Is in the Air—Inhaled Gases on Their Way to the Neurons

Author: Stefanie Scheid, Ulrich Goebel, and Felix Ulbrich
Subjects: neuronal cell death, ischemia/reperfusion injury, volatile anesthetics, noble gases, isoflurane, sevoflurane, Cytology, QH573-671
Abstract: Cerebral injury is a leading cause of long-term disability and mortality. Common causes include major cardiovascular events, such as cardiac arrest, ischemic stroke, and subarachnoid hemorrhage, traumatic brain injury, and neurodegenerative as well as neuroinflammatory disorders. Despite improvements in pharmacological and interventional treatment options, due to the brain’s limited regeneration potential, survival is often associated with the impairment of crucial functions that lead to occupational inability and enormous economic burden. For decades, researchers have therefore been investigating adjuvant therapeutic options to alleviate neuronal cell death. Although promising in preclinical studies, a huge variety of drugs thought to provide neuroprotective effects failed in clinical trials. However, utilizing medical gases, noble gases, and gaseous molecules as supportive treatment options may offer new perspectives for patients suffering neuronal damage. This review provides an overview of current research, potentials and mechanisms of these substances as a promising therapeutic alternative for the treatment of cerebral injury.
Published: 2023
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6. Diagnosing capillary leak in critically ill patients: development of an innovative scoring instrument for non-invasive detection

Author: Jakob Wollborn, Lars O. Hassenzahl, Daniel Reker, Hans Felix Staehle, Anne Marie Omlor, Wolfgang Baar, Kai B. Kaufmann, Felix Ulbrich, Christian Wunder, Stefan Utzolino, Hartmut Buerkle, Johannes Kalbhenn, Sebastian Heinrich, and Ulrich Goebel
Subjects: Capillary leak syndrome, Critical care, Sepsis, Fluid balance, Endothelial permeability, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The concomitant occurrence of the symptoms intravascular hypovolemia, peripheral edema and hemodynamic instability is typically named Capillary Leak Syndrome (CLS) and often occurs in surgical critical ill patients. However, neither a unitary definition nor standardized diagnostic criteria exist so far. We aimed to investigate common characteristics of this phenomenon with a subsequent scoring system, determining whether CLS contributes to mortality. Methods We conducted this single-center, observational, multidisciplinary, prospective trial in two separately run surgical ICUs of a tertiary academic medical center. 200 surgical patients admitted to the ICU and 30 healthy volunteers were included. Patients were clinically diagnosed as CLS or No-CLS group (each N = 100) according to the grade of edema, intravascular hypovolemia, hemodynamic instability, and positive fluid balance by two independent attending physicians with > 10 years of experience in ICU. We performed daily measurements with non-invasive body impedance electrical analysis, ultrasound and analysis of serum biomarkers to generate objective diagnostic criteria. Receiver operating characteristics were used, while we developed machine learning models to increase diagnostic specifications for our scoring model. Results The 30-day mortility was increased among CLS patients (12 vs. 1%, P = 0.002), while showing higher SOFA-scores. Extracellular water was increased in patients with CLS with higher echogenicity of subcutaneous tissue [29(24–31) vs. 19(16–21), P
Published: 2021
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7. Argon reduces microglial activation and inflammatory cytokine expression in retinal ischemia/reperfusion injury

Author: Ulrich Goebel, Stefanie Scheid, Sashko Spassov, Nils Schallner, Jakob Wollborn, Hartmut Buerkle, and Felix Ulbrich
Subjects: argon, ischemia/reperfusion injury, microglia, neuroinflammation, neuroprotection, noble gas, sh-sy5y, toll-like receptor, transcription factor, Neurology. Diseases of the nervous system, RC346-429
Abstract: We previously found that argon exerts its neuroprotective effect in part by inhibition of the toll-like receptors (TLR) 2 and 4. The downstream transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB) are also affected by argon and may play a role in neuroprotection. It also has been demonstrated that argon treatment could mitigate brain damage, reduce excessive microglial activation, and subsequently attenuate brain inflammation. Despite intensive research, the further exact mechanism remains unclear. In this study, human neuroblastoma cells were damaged in vitro with rotenone over a period of 4 hours (to mimic cerebral ischemia and reperfusion damage), followed by a 2-hour post-conditioning with argon (75%). In a separate in vivo experiment, retinal ischemia/reperfusion injury was induced in rats by increasing intraocular pressure for 1 hour. Upon reperfusion, argon was administered by inhalation for 2 hours. Argon reduced the binding of the transcription factors signal transducer and activator of transcription 3, nuclear factor kappa B, activator protein 1, and nuclear factor erythroid 2-related factor 2, which are involved in regulation of neuronal damage. Flow cytometry analysis showed that argon downregulated the Fas ligand. Some transcription factors were regulated by toll-like receptors; therefore, their effects could be eliminated, at least in part, by the TLR2 and TLR4 inhibitor oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC). Argon treatment reduced microglial activation after retinal ischemia/reperfusion injury. Subsequent quantitative polymerase chain reaction analysis revealed a reduction in the pro-inflammatory cytokines interleukin (IL-1α), IL-1β, IL-6, tumor necrosis factor α, and inducible nitric oxide synthase. Our results suggest that argon reduced the extent of inflammation in retinal neurons after ischemia/reperfusion injury by suppression of transcription factors crucial for microglial activation. Argon has no known side effects or narcotic properties; therefore, therapeutic use of this noble gas appears ideal for treatment of patients with neuronal damage in retinal ischemia/reperfusion injury. The animal experiments were approved by the Commission for Animal Care of the University of Freiburg (approval No. 35-9185.81/G14-122) on October 19, 2012.
Published: 2021
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8. LMA Gastro™ airway is feasible during upper gastrointestinal interventional endoscopic procedures in high risk patients: a single-center observational study

Author: Axel Schmutz, Thomas Loeffler, Arthur Schmidt, and Ulrich Goebel
Subjects: Achalasia, Endoscopic procedures, Endoscopic submucosal dissection, High-risk patients, Supraglottic airway device, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background Nonoperating room anesthesia during gastroenterological procedures is a growing field in anesthetic practice. While the numbers of patients with severe comorbidities are rising constantly, gastrointestinal endoscopic interventions are moving closer to minimally invasive endoscopic surgery. The LMA Gastro™ is a new supraglottic airway device, developed specifically for upper gastrointestinal endoscopy and interventions. The aim of this study was to evaluate the feasibility of LMA Gastro™ in patients with ASA physical status ≥3 undergoing advanced endoscopic procedures. Methods We analyzed data from 214 patients retrospectively who received anesthesia for gastroenterological interventions. Inclusion criteria were upper gastrointestinal endoscopic interventions, airway management with LMA Gastro™ and ASA status ≥3. The primary outcome measure was successful use of LMA Gastro™ for airway management and endoscopic intervention. Results Thirtyone patients with ASA physical status ≥3, undergoing complex and prolonged upper gastrointestinal endoscopic procedures were included. There were 7 endoscopic retrograde cholangiopancreatographies, 7 peroral endoscopic myotomies, 5 percutaneous endoscopic gastrostomies and 12 other complex procedures (e.g. endoscopic submucosal dissection, esophageal stent placement etc.). Of these, 27 patients were managed successfully using the LMA Gastro™. Placement of the LMA Gastro™ was reported as easy. Positive pressure ventilation was performed without difficulty. The feasibility of the LMA Gastro™ for endoscopic intervention was rated excellent by the endoscopists. In four patients, placement or ventilation with LMA Gastro™ was not possible. Conclusions We demonstrated the feasibility of the LMA Gastro™ during general anesthesia for advanced endoscopic procedures in high-risk patients. Trial registration German Clinical Trials Register ( DRKS00017396 ) Date of registration: 23rd May 2019, retrospectively registered.
Published: 2020
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9. Carbon monoxide in intensive care medicine—time to start the therapeutic application?!

Author: Ulrich Goebel and Jakob Wollborn
Subjects: Carbon monoxide, Haeme-oxygenase-1, Acute respiratory distress syndrome, Idiopathic pulmonary fibrosis, Acute kidney injury, Extracorporeal circulation, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Carbon monoxide (CO) is not only known as a toxic gas due to its characteristics as an odorless molecule and its rapid binding to haem-containing molecules, thus inhibiting the respiratory chain in cells resulting in hypoxia. For decades, scientists established evidence about its endogenously production in the breakdown of haem via haem-oxygenase (HO-1) and its physiological effects. Among these, the modulation of various systems inside the body are well described (e.g., anti-inflammatory, anti-oxidative, anti-apoptotic, and anti-proliferative). Carbon monoxide is able to modulate several extra- and intra-cellular signaling molecules leading to differentiated response according to the specific stimulus. With our growing understanding in the way CO exerts its effects, especially in the mitochondria and its intracellular pathways, it is tempting to speculate about a clinical application of this substance. Since HO-1 is not easy to induce, research focused on the application of the gaseous molecule CO by itself or the implementation of carbon monoxide releasing molecules (CO-RM) to deliver the molecule at a time- and dose dependently safe way to any target organ. After years of research in cellular systems and animal models, summing up data about safety issues as well as possible target to treat in various diseases, the first feasibility trials in humans were established. Up-to-date, safety issues have been cleared for low-dose carbon monoxide inhalation (up to 500 ppm), while there is no clinical data regarding the injection or intake of any kind of CO-RM so far. Current models of human research include sepsis, acute lung injury, and acute respiratory distress syndrome as well as acute kidney injury. Carbon monoxide is a most promising candidate in terms of a therapeutic agent to improve outbalanced organ conditions. In this paper, we summarized the current understanding of carbon monoxide’s biology and its possible organ targets to treating the critically ill patients in tomorrow’s ICU.
Published: 2020
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10. Epidural analgesia and avoidance of blood transfusion are associated with reduced mortality in patients with postoperative pulmonary complications following thoracotomic esophagectomy: a retrospective cohort study of 335 patients

Author: Kai B. Kaufmann, Wolfgang Baar, Torben Glatz, Jens Hoeppner, Hartmut Buerkle, Ulrich Goebel, and Sebastian Heinrich
Subjects: Esophagectomy, Postoperative pulmonary complications, Thoracic epidural anesthesia, Blood transfusion, Independent risk factors, 90-days mortality, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background Postoperative pulmonary complications (PPCs) represent the most frequent complications after esophagectomy. The aim of this study was to identify modifiable risk factors for PPCs and 90-days mortality related to PPCs after esophagectomy in esophageal cancer patients. Methods This is a single center retrospective cohort study of 335 patients suffering from esophageal cancer who underwent esophagectomy between 1996 and 2014 at a university hospital center. Statistical processing was conducted using univariate and multivariate stepwise logistic regression analysis of patient-specific and procedural risk factors for PPCs and mortality. Results The incidence of PPCs was 52% (175/335) and the 90-days mortality rate of patients with PPCs was 8% (26/335) in this study cohort. The univariate and multivariate analysis revealed the following independent risk factors for PPCs and its associated mortality. ASA score ≥ 3 was the only independent patient-specific risk factor for the incidence of PPCs and 90-days mortality of patients with an odds ratio for PPCs being 1.7 (1.1–2.6 95% CI) and an odds ratio of 2.6 (1.1–6.2 95% CI) for 90-days mortality. The multivariate approach depicted two independent procedural risk factors including transfusion of packed red blood cells (PRBCs) odds ratio of 1.9 (1.2–3 95% CI) for PPCs and an odds ratio of 5.0 (2.0–12.6 95% CI) for 90-days mortality; absence of thoracic epidural anesthesia (TEA) revealed the highest odds ratio 2.0 (1.01–3.8 95% CI) for PPCs and an odds ratio of 3.9 (1.6–9.7 95% CI) for 90-days mortality. Conclusion In esophageal cancer patients undergoing esophagectomy via thoracotomy, epidural analgesia and the avoidance of intraoperative blood transfusion are significantly associated with a reduced 90-days mortality related to PPCs.
Published: 2019
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11. Reply to: Scoring the capillary leak syndrome: towards an individualized gradation of the vascular barrier injury

Author: Jakob Wollborn and Ulrich Goebel
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2022
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12. Lower rate of delayed graft function is observed when epidural analgesia for living donor nephrectomy is administered

Author: Wolfgang Baar, Ulrich Goebel, Hartmut Buerkle, Bernd Jaenigen, Kai Kaufmann, and Sebastian Heinrich
Subjects: Kidney transplantation, Delayed graft function, Epidural analgesia, Donor nephrectomy, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background The beneficial effects of epidural analgesia (EDA) in terms of pain control and postoperative convalescence are widely known and led to a frequent use for patients who underwent living donor kidney nephrectomy. The objective of this study was to determine whether general anesthesia (GA) plus EDA compared to GA only, administered for living donor nephrectomy has effects on postoperative graft function in recipients. Methods In this monocentric, retrospective cohort analysis we analyzed the closed files of all consecutive donor- recipient pairs who underwent living donor kidney transplantations from 2008 to 2017. The outcome variable was delayed graft function (DGF), defined as at least one hemodialysis within seven days postoperatively, once hyperacute rejection, vascular or urinary tract complications were ruled out. Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher exact test for categorical variables with a significance level of p
Published: 2019
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13. Dorsal recruitment with flow-controlled expiration (FLEX): an experimental study in mechanically ventilated lung-healthy and lung-injured pigs

Author: Silke Borgmann, Johannes Schmidt, Ulrich Goebel, Joerg Haberstroh, Josef Guttmann, and Stefan Schumann
Subjects: Acute respiratory distress syndrome, Electrical impedance tomography, Oleic acid, Positive pressure ventilation, Expiration control, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Concepts for optimizing mechanical ventilation focus mainly on modifying the inspiratory phase. We propose flow-controlled expiration (FLEX) as an additional means for lung protective ventilation and hypothesize that it is capable of recruiting dependent areas of the lungs. This study investigates potential recruiting effects of FLEX using models of mechanically ventilated pigs before and after induction of lung injury with oleic acid. Methods Seven pigs in the supine position were ventilated with tidal volume 8 ml·kg− 1 and positive end-expiratory pressure (PEEP) set to maintain partial pressure of oxygen in arterial blood (paO2) at ≥ 60 mmHg and monitored with electrical impedance tomography (EIT). Two ventilation sequences were recorded - one before and one after induction of lung injury. Each sequence comprised 2 min of conventional volume-controlled ventilation (VCV), 2 min of VCV with FLEX and 1 min again of conventional VCV. Analysis of the EIT recordings comprised global and ventral and dorsal baseline levels of impedance curves, end-expiratory no-flow periods, tidal variation in ventral and dorsal areas, and regional ventilation delay index. Results With FLEX, the duration of the end-expiratory zero flow intervals was significantly shortened (VCV 1.4 ± 0.3 s; FLEX 0.7 ± 0.1 s, p
Published: 2018
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14. Evaluation of hemodynamic goal-directed therapy to reduce the incidence of bone cement implantation syndrome in patients undergoing cemented hip arthroplasty – a randomized parallel-arm trial

Author: Kai B. Kaufmann, Wolfgang Baar, Judith Rexer, Thomas Loeffler, Sebastian Heinrich, Lukas Konstantinidis, Hartmut Buerkle, and Ulrich Goebel
Subjects: Hip arthroplasty, Postoperative complications, Hemodynamics, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background The bone cement implantation syndrome (BCIS) is a frequent and potentially disastrous intraoperative complication in patients undergoing cemented hip arthroplasty. Several risk factors have been identified, however randomized controlled trials to reduce the incidence of BCIS are still pending. We hypothesized that goal-directed hemodynamic therapy guided by esophageal Doppler monitoring (EDM) may reduce the incidence of BCIS in a randomized, controlled parallel-arm trial. Methods After approval of the local ethics committee, 90 patients scheduled for cemented hip arthroplasty at the Medical Center – University of Freiburg were randomly assigned to either standard hemodynamic management or goal-directed therapy (GDT) guided by an esophageal Doppler monitoring-based algorithm. The primary endpoint was the incidence of overall BCIS including grade 1–3 after cementation of the femoral stem. Secondary endpoints included cardiac function, length of hospital stay and postoperative complications. Results Ninety patients were finally analyzed. With regards to the primary endpoint, the overall incidence of BCIS showed no difference between the GDT and control group. Compared to the control group, patients of the GDT group showed a higher cardiac index before and after bone cement implantation (2.7 vs. 2.2 [l●min− 1●m− 2]; 2.8 vs. 2.4 [l●min− 1●m− 2]; P = 0.003, P = 0.042), whereas intraoperative amount of fluids and mean arterial pressure did not differ. Conclusions The implementation of a specific hemodynamic goal-directed therapy did not reduce the overall incidence of BCIS in patients undergoing cemented hip arthroplasty. Trial registration This randomized clinical two-arm parallel study was approved by the local Ethics Committee, Freiburg, Germany [EK 160/15, PI: U. Goebel] and registered in the German Clinical Trials Register (DRKS No. 00008778, 16th of June, 2015).
Published: 2018
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15. The Carbon monoxide releasing molecule ALF-186 mediates anti-inflammatory and neuroprotective effects via the soluble guanylate cyclase ß1 in rats’ retinal ganglion cells after ischemia and reperfusion injury

Author: Felix Ulbrich, Claus Hagmann, Hartmut Buerkle, Carlos C. Romao, Nils Schallner, Ulrich Goebel, and Julia Biermann
Subjects: Ischemia/reperfusion injury, Carbon monoxide, Neuro-inflammation, Neuroprotection, sGC-ß1, Heat shock proteins, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background The endogenously produced gaseous molecule carbon monoxide is able to promote organ protection after ischemia-reperfusion injuries (IRI). The impact of carbon monoxide releasing molecules (CORM) regarding inflammation in neuronal tissues has not been studied in detail. In this investigation, we aimed to analyze the effects of the CORM ALF-186 on neuro-inflammation and hypothesized that the soluble guanylate cyclase (sGC) is playing a decisive role. Methods Retinal ischemia-reperfusion injury was performed for 60 min in Sprague-Dawley rats. Thereafter, the CORM ALF-186 (10 mg/kg) in the presence or absence of the sGC inhibitor ODQ was injected via a tail vein. Retinal tissue was harvested 24 h later to analyze mRNA or protein expression of sGC-β1 subunit, transcription factors NF-κB and CREB, the inflammatory cytokines TNF-α and IL-6, as well as the heat shock proteins (HSP) HSP-70 and HSP-90. Immunohistochemistry was performed on frozen sections of the retina. The overall neuroprotective effect of ALF-186 was assessed by counting fluorogold-pre-labeled retinal ganglion cells (RGC) 7 days after IRI. Results Ischemia-reperfusion mediated loss of vital RGC was attenuated by the administration of ALF-186 after injury. ALF-186 treatment after IRI induced sGC-ß1 leading to a decreased NF-κB and CREB phosphorylation. Consecutively, ALF-186 mitigated IRI induced TNF-α and IL-6 expression in the retina and in the rats’ serum. Moreover, ALF-186 attenuated heat shock protein 70 (Hsp-70) while increasing Hsp-90. The sGC-inhibitor ODQ attenuated the anti-inflammatory effects of ALF-186 and increased retinal loss of ganglion cells. These results were confirmed by immunohistochemistry. Conclusion The CORM ALF-186 protected RGC from IRI induced loss. Furthermore, ALF-186 reduced IRI mediated neuroinflammation in the retina and in the serum by activating sGC. Inhibition of sGC stopped the beneficial and protective effects of ALF-186. ALF-186 may present a promising therapeutic alternative in treating inflammation after neuronal IRI.
Published: 2017
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16. An easy-to-build, low-budget point-of-care ultrasound simulator: from Linux to a web-based solution

Author: Domagoj Damjanovic, Ulrich Goebel, Benedikt Fischer, Martin Huth, Hartmut Breger, Hartmut Buerkle, and Axel Schmutz
Subjects: Ultrasonography, Point-of-care systems, Simulation training, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract: Abstract Background Hands-on training in point-of-care ultrasound (POC-US) should ideally comprise bedside teaching, as well as simulated clinical scenarios. High-fidelity phantoms and portable ultrasound simulation systems are commercially available, however, at considerable costs. This limits their suitability for medical schools. A Linux-based software for Emergency Department Ultrasound Simulation (edus2TM) was developed by Kulyk and Olszynski in 2011. Its feasibility for POC-US education has been well-documented, and shows good acceptance. An important limitation to an even more widespread use of edus2, however, may be due to the need for a virtual machine for WINDOWS® systems. Our aim was to adapt the original software toward an HTML-based solution, thus making it affordable and applicable in any simulation setting. Methods We created an HTML browser-based ultrasound simulation application, which reads the input of different sensors, triggering an ultrasound video to be displayed on a respective device. RFID tags, NFC tags, and QR Codes™ have been integrated into training phantoms or were attached to standardized patients. The RFID antenna was hidden in a mock ultrasound probe. The application is independent from the respective device. Results Our application was used successfully with different trigger/scanner combinations and mounted readily into simulated training scenarios. The application runs independently from operating systems or electronic devices. Conclusion This low-cost, browser-based ultrasound simulator is easy-to-build, very adaptive, and independent from operating systems. It has the potential to facilitate POC-US training throughout the world, especially in resource-limited areas.
Published: 2017
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17. Perioperative cytokine profile during lung surgery predicts patients at risk for postoperative complications-A prospective, clinical study.

Author: Kai B Kaufmann, Sebastian Heinrich, Hans Felix Staehle, Lioudmila Bogatyreva, Hartmut Buerkle, and Ulrich Goebel
Subjects: Medicine, Science
Abstract: BackgroundPostoperative complications after lung surgery are frequent, having a detrimental effect on patients' further course. Complications may lead to an increased length of hospital stay and cause additional costs. Several risk factors have been identified but it is still difficult to predict contemporary which patients are at risk. We hypothesized that patients who show an increased inflammatory response at the time of wound closure and 24 hours after surgery are at risk of postoperative complications within 30 days after surgery.MethodsPostoperative complications (pulmonary, cardiac, neurological and renal) of 96 patients scheduled for lung surgery at the Medical Center-University of Freiburg were analyzed in this prospective, clinical study. Blood samples for cytokine analysis (Interleukin (IL)-6, IL-8, IL-10, Tumor necrosis factor [TNF]-α, IL-1ß and IL12p70) were taken before surgery, at wound closure and 24 hours after surgery. Cytokine levels of patients with and without postoperative complications were analyzed by Receiver operating characteristic (ROC) curve analysis. To adjust the results according to existing covariates a multivariate logistic regression analysis was conducted.ResultsThe complication and non-complication group differed significantly according to nicotine dependency, Angiotensin-receptor-II blocker medication, rate of thoracotomy and preoperative lung function. The intraoperative hemodynamic parameters and therapy did not differ between the groups. Twenty-nine patients (30%) developed postoperative complications within 30 days after surgery. Plasma concentrations of IL-6, IL-10 and IL-8 at the time of wound closure and 24 hours after surgery were higher in the complication group. Multivariate regression analysis on postoperative complications revealed an Odds ratio of 56 for patients with IL-6 and IL-8 levels above the 3rd quartile measured on the first postoperative day.ConclusionsPerioperative detection of increased plasma concentrations of inflammatory cytokines in lung surgery may be used in addition to other clinical predictors to identify patients at risk for postoperative complications.Trial registrationGerman Clinical Trials Register 00006961.
Published: 2018
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18. Somatosensory and transcranial motor evoked potential monitoring in a porcine model for experimental procedures.

Author: Sven Maier, Ulrich Goebel, Sonja Krause, Christoph Benk, Martin A Schick, Hartmut Buerkle, Friedhelm Beyersdorf, Fabian A Kari, and Jakob Wollborn
Subjects: Medicine, Science
Abstract: Evoked potential monitoring has evolved as an essential tool not only for elaborate neurological diagnostics, but also for general clinical practice. Moreover, it is increasingly used to guide surgical procedures and prognosticate neurological outcome in the critical care unit, e.g. after cardiac arrest. Experimental animal models aim to simulate a human-like scenario to deduct relevant clinical information for patient treatment and to test novel therapeutic opportunities. Porcine models are particularly ideal due to a comparable cardiovascular system and size. However, certain anatomic disparities have to be taken into consideration when evoked potential monitoring is used in animal models. We describe a non-invasive and reproducible set-up useful for different modalities in porcine models. We further illustrate hints to overcome multi-faceted problems commonly occurring while using this sophisticated technique. Our descriptions can be used to answer a plethora of experimental questions, and help to further facilitate experimental therapeutic innovation.
Published: 2018
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19. Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release.

Author: Julia Stifter, Felix Ulbrich, Ulrich Goebel, Daniel Böhringer, Wolf Alexander Lagrèze, and Julia Biermann
Subjects: Medicine, Science
Abstract: Retinal ischemia induces apoptosis leading to neurodegeneration and vision impairment. Carbon monoxide (CO) in gaseous form showed cell-protective and anti-inflammatory effects after retinal ischemia-reperfusion-injury (IRI). These effects were also demonstrated for the intravenously administered CO-releasing molecule (CORM) ALF-186. This article summarizes the results of intravitreally released CO to assess its suitability as a neuroprotective and neuroregenerative agent.Water-soluble CORM ALF-186 (25 μg), PBS, or inactivated ALF (iALF) (all 5 μl) were intravitreally applied into the left eyes of rats directly after retinal IRI for 1 h. Their right eyes remained unaffected and were used for comparison. Retinal tissue was harvested 24 h after intervention to analyze mRNA or protein expression of Caspase-3, pERK1/2, p38, HSP70/90, NF-kappaB, AIF-1 (allograft inflammatory factor), TNF-α, and GAP-43. Densities of fluorogold-prelabeled retinal ganglion cells (RGC) were examined in flat-mounted retinae seven days after IRI and were expressed as mean/mm2. The ability of RGC to regenerate their axon was evaluated two and seven days after IRI using retinal explants in laminin-1-coated cultures. Immunohistochemistry was used to analyze the different cell types growing out of the retinal explants.Compared to the RGC-density in the contralateral right eyes (2804±214 RGC/mm2; data are mean±SD), IRI+PBS injection resulted in a remarkable loss of RGC (1554±159 RGC/mm2), p
Published: 2017
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20. The CORM ALF-186 Mediates Anti-Apoptotic Signaling via an Activation of the p38 MAPK after Ischemia and Reperfusion Injury in Retinal Ganglion Cells.

Author: Felix Ulbrich, Kai B Kaufmann, Alexander Meske, Wolf A Lagrèze, Michael Augustynik, Hartmut Buerkle, Carlos C Ramao, Julia Biermann, and Ulrich Goebel
Subjects: Medicine, Science
Abstract: Ischemia and reperfusion injury may induce apoptosis and lead to sustained tissue damage and loss of function, especially in neuronal organs. While carbon monoxide is known to exert protective effects after various harmful events, the mechanism of carbon monoxide releasing molecules in neuronal tissue has not been investigated yet. We hypothesize that the carbon monoxide releasing molecule (CORM) ALF-186, administered after neuronal ischemia-reperfusion injury (IRI), counteracts retinal apoptosis and its involved signaling pathways and consecutively reduces neuronal tissue damage.IRI was performed in rat´s retinae for 1 hour. The water-soluble CORM ALF-186 (10 mg/kg) was administered intravenously via a tail vein after reperfusion. After 24 and 48 hours, retinal tissue was harvested to analyze mRNA and protein expression of Bcl-2, Bax, Caspase-3, ERK1/2, p38 and JNK. Densities of fluorogold pre-labeled retinal ganglion cells (RGC) were analyzed 7 days after IRI. Immunohistochemistry was performed on retinal cross sections.ALF-186 significantly reduced IRI mediated loss of RGC. ALF-186 treatment differentially affected mitogen-activated protein kinases (MAPK) phosphorylation: ALF-186 activated p38 and suppressed ERK1/2 phosphorylation, while JNK remained unchanged. Furthermore, ALF-186 treatment affected mitochondrial apoptosis, decreasing pro-apoptotic Bax and Caspase-3-cleavage, but increasing anti-apoptotic Bcl-2. Inhibition of p38-MAPK using SB203580 reduced ALF-186 mediated anti-apoptotic effects.In this study, ALF-186 mediated substantial neuroprotection, affecting intracellular apoptotic signaling, mainly via MAPK p38. CORMs may thus represent a promising therapeutic alternative treating neuronal IRI.
Published: 2016
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21. The Cytoprotective Effects of E-α-(4-Methoxyphenyl)-2',3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC)--A Novel and Non-Cytotoxic HO-1 Inducer.

Author: Kai B Kaufmann, Nafisah Al-Rifai, Felix Ulbrich, Nils Schallner, Hannelore Rücker, Monika Enzinger, Hermina Petkes, Sebastian Pitzl, Ulrich Goebel, and Sabine Amslinger
Subjects: Medicine, Science
Abstract: Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1), is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2',3,4,4'-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS) production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2'-hydroxychalcone, calythropsin and 2'-hydroxy-3,4,4'-trimethoxychalcone) prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl)-2',3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC) demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264.7 macrophages. The observed cytoprotective effect may partly be related to both, the activation of the Nrf2- and inhibition of the NF-κB pathway.
Published: 2015
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22. Argon Mediates Anti-Apoptotic Signaling and Neuroprotection via Inhibition of Toll-Like Receptor 2 and 4.

Author: Felix Ulbrich, Kai Kaufmann, Martin Roesslein, Franziska Wellner, Volker Auwärter, Jürgen Kempf, Torsten Loop, Hartmut Buerkle, and Ulrich Goebel
Subjects: Medicine, Science
Abstract: Recently, the noble gas argon attracted significant attention due to its neuroprotective properties. However, the underlying molecular mechanism is still poorly understood. There is growing evidence that the extracellular regulated kinase 1/2 (ERK1/2) is involved in Argon´s protective effect. We hypothesized that argon mediates its protective effects via the upstream located toll-like receptors (TLRs) 2 and 4.Apoptosis in a human neuroblastoma cell line (SH-SY5Y) was induced using rotenone. Argon treatment was performed after induction of apoptosis with different concentrations (25, 50 and 75 Vol% in oxygen 21 Vol%, carbon dioxide and nitrogen) for 2 or 4 hours respectively. Apoptosis was analyzed using flow cytometry (annexin-V (AV)/propidiumiodide (PI)) staining, caspase-3 activity and caspase cleavage. TLR density on the cells' surface was analyzed using FACS and immunohistochemistry. Inhibition of TLR signaling and extracellular regulated kinase 1/2 (ERK1/2) were assessed by western blot, activity assays and FACS analysis.Argon 75 Vol% treatment abolished rotenone-induced apoptosis. This effect was attenuated dose- and time-dependently. Argon treatment was accompanied with a significant reduction of TLR2 and TLR4 receptor density and protein expression. Moreover, argon mediated increase in ERK1/2 phosphorylation was attenuated after inhibition of TLR signaling. ERK1/2 and TLR signaling inhibitors abolished the anti-apoptotic and cytoprotective effects of argon. Immunohistochemistry results strengthened these findings.These findings suggest that argon-mediated anti-apoptotic and neuroprotective effects are mediated via inhibition of TLR2 and TLR4.
Published: 2015
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23. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

Author: Felix Ulbrich, Nils Schallner, Mark Coburn, Torsten Loop, Wolf Alexander Lagrèze, Julia Biermann, and Ulrich Goebel
Subjects: Medicine, Science
Abstract: Retinal ischemia and reperfusion injuries (IRI) permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC) of the rat's eye.IRI was performed on the left eyes of rats (n = 8) with or without inhaled Argon postconditioning (25, 50 and 75 Vol%) for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours). Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA.IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p
Published: 2014
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24. Carbon monoxide abrogates ischemic insult to neuronal cells via the soluble guanylate cyclase-cGMP pathway.

Author: Nils Schallner, Carlos C Romão, Julia Biermann, Wolf A Lagrèze, Leo E Otterbein, Hartmut Buerkle, Torsten Loop, and Ulrich Goebel
Subjects: Medicine, Science
Abstract: Carbon monoxide (CO) is an accepted cytoprotective molecule. The extent and mechanisms of protection in neuronal systems have not been well studied. We hypothesized that delivery of CO via a novel releasing molecule (CORM) would impart neuroprotection in vivo against ischemia-reperfusion injury (IRI)-induced apoptosis of retinal ganglion cells (RGC) and in vitro of neuronal SH-SY5Y-cells via activation of soluble guanylate-cyclase (sGC).To mimic ischemic respiratory arrest, SH-SY5Y-cells were incubated with rotenone (100 nmol/L, 4 h) ± CORM ALF186 (10-100 µmol/L) or inactivated ALF186 lacking the potential of releasing CO. Apoptosis and reactive oxygen species (ROS) production were analyzed using flow-cytometry (Annexin V, mitochondrial membrane potential, CM-H2DCFDA) and Western blot (Caspase-3). The impact of ALF186± respiratory arrest on cell signaling was assessed by measuring expression of nitric oxide synthase (NOS) and soluble guanylate-cyclase (sGC) and by analyzing cellular cGMP levels. The effect of ALF186 (10 mg/kg iv) on retinal IRI in Sprague-Dawley rats was assessed by measuring densities of fluorogold-labeled RGC after IRI and by analysis of apoptosis-related genes in retinal tissue.ALF186 but not inactivated ALF186 inhibited rotenone-induced apoptosis (Annexin V positive cells: 25 ± 2% rotenone vs. 14 ± 1% ALF186+rotenone, p
Published: 2013
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25. Correction: Carbon Monoxide Abrogates Ischemic Insult to Neuronal Cells via the Soluble Guanylate Cyclase-cGMP Pathway.

Author: Nils Schallner, Carlos C. Romão, Julia Biermann, Wolf A. Lagrèze, Leo E. Otterbein, Hartmut Buerkle, Torsten Loop, and Ulrich Goebel
Subjects: Medicine, Science
Published: 2013
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26. Postconditioning with inhaled carbon monoxide counteracts apoptosis and neuroinflammation in the ischemic rat retina.

Author: Nils Schallner, Matthias Fuchs, Christian I Schwer, Torsten Loop, Hartmut Buerkle, Wolf Alexander Lagrèze, Christian van Oterendorp, Julia Biermann, and Ulrich Goebel
Subjects: Medicine, Science
Abstract: Ischemia and reperfusion injury (I/R) of neuronal structures and organs is associated with increased morbidity and mortality due to neuronal cell death. We hypothesized that inhalation of carbon monoxide (CO) after I/R injury ('postconditioning') would protect retinal ganglion cells (RGC).Retinal I/R injury was performed in Sprague-Dawley rats (n = 8) by increasing ocular pressure (120 mmHg, 1 h). Rats inhaled room air or CO (250 ppm) for 1 h immediately following ischemia or with 1.5 and 3 h latency. Retinal tissue was harvested to analyze Bcl-2, Bax, Caspase-3, HO-1 expression and phosphorylation of the nuclear transcription factor (NF)-κB, p38 and ERK-1/2 MAPK. NF-κB activation was determined and inhibition of ERK-1/2 was performed using PD98059 (2 mg/kg). Densities of fluorogold prelabeled RGC were analyzed 7 days after injury. Microglia, macrophage and Müller cell activation and proliferation were evaluated by Iba-1, GFAP and Ki-67 staining.Inhalation of CO after I/R inhibited Bax and Caspase-3 expression (Bax: 1.9 ± 0.3 vs. 1.4 ± 0.2, p = 0.028; caspase-3: 2.0 ± 0.2 vs. 1.5 ± 0.1, p = 0.007; mean ± S.D., fold induction at 12 h), while expression of Bcl-2 was induced (1.2 ± 0.2 vs. 1.6 ± 0.2, p = 0.001; mean ± S.D., fold induction at 12 h). CO postconditioning suppressed retinal p38 phosphorylation (p = 0.023 at 24 h) and induced the phosphorylation of ERK-1/2 (p
Published: 2012
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27. Argon: a novel therapeutic option to treat neuronal ischemia and reperfusion injuries?

Author: Felix Ulbrich and Ulrich Goebel
Subjects: Neurology. Diseases of the nervous system, RC346-429
Published: 2015
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28. Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia

Author: Anja Troeger, Meinolf Siepermann, Gabriele Escherich, Roland Meisel, Reinhardt Willers, Sonja Gudowius, Thomas Moritz, Hans-Juergen Laws, Helmut Hanenberg, Ulrich Goebel, Gritta E. Janka-Schaub, Csaba Mahotka, and Dagmar Dilloo
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Background and Objectives Impaired apoptosis, mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin, is thought to contribute to leukemic cell survival. In contrast to low expression of survivin in normal differentiated adult tissues, very high levels of survivin have been described in a number of different tumors. Overexpression of survivin was found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. To date, however, there is no information available on the prognostic role of survivin in pediatric precursor B-cell acute lymphocytic leukemia (BCP-ALL), the most frequent malignancy in childhood.Design and Methods In a retrospective study including 66 pediatric patients we analyzed the impact of survivin protein levels on outcome in BCP-ALL.Results Survivin overexpression, with an up to ten-fold increase of the normal level, was detected in 65% of the leukemic samples in contrast to negligible expression in non-malignant hematopoietic cells. Despite considerable variety of expression levels in ALL cells, there was no association of survivin levels with established risk factors. However, patients suffering relapse of disease or death had significantly higher survivin expression than those with a favorable outcome. Overexpression of survivin is a significant prognostic marker for 3 year relapse free, event-free and overall survival, again independent of the established prognostic factors in ALL, such as age and leukocyte count at diagnosis as assessed in multivariate analysis.Interpretation and Conclusions Overexpression of survivin in BCP-ALL identifies patients with a high risk of early relapse. Upon confirmation in a prospective analysis, survivin expression may, in the future, serve to further refine treatment stratification with intensification of therapy in those patients prone to relapse.
Published: 2007
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29. Argon preconditioning protects neuronal cells with a Toll-like receptor-mediated effect

Author: Felix Ulbrich, Stefanie Scheid, Adrien Lejarre, Jakob Wollborn, Hartmut Buerkle, and Ulrich Goebel
Subjects: Developmental Neuroscience
Abstract: The noble gas argon has the potential to protect neuronal cells from cell death. So far, this effect has been studied in treatment after acute damage. Preconditioning using argon has not yet been investigated. In this study, human neuroblastoma SH-SY5Y cells were treated with different concentrations of argon (25%, 50%, and 74%; 21% O
Published: 2022

30. Correction to: Increased 30-day mortality in very old ICU patients with COVID-19 compared to patients with respiratory failure without COVID-19

Author: Maurizio Cecconi, Hans Flaatten, Wojciech Szczeklik, Kyrillos Nassim, Stephane Dauger, Georg Goebel, Joerg C. Schefold, Hazem Abosheaishaa, Dylan De Lange, Ulrich Goebel, Christian Jung, Samar Tharwat, and Walter Swinnen
Subjects: Critical Care and Intensive Care Medicine
Published: 2022
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31. Argon reduces microglial activation and inflammatory cytokine expression in retinal ischemia/reperfusion injury

Author: Ulrich Goebel, Nils Schallner, Hartmut Buerkle, Jakob Wollborn, Felix Ulbrich, Sashko Spassov, and Stefanie Scheid
Subjects: 0301 basic medicine, noble gas, Ischemia, microglia, Inflammation, Pharmacology, ischemia/reperfusion injury, SH-SY5Y, Neuroprotection, lcsh:RC346-429, neuroinflammation, 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, argon, neuroprotection, sh-sy5y, toll-like receptor, transcription factor, medicine, STAT3, Transcription factor, lcsh:Neurology. Diseases of the nervous system, biology, Chemistry, medicine.disease, Nitric oxide synthase, 030104 developmental biology, STAT protein, biology.protein, medicine.symptom, Reperfusion injury, 030217 neurology & neurosurgery, Research Article
Abstract: We previously found that argon exerts its neuroprotective effect in part by inhibition of the toll-like receptors (TLR) 2 and 4. The downstream transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB) are also affected by argon and may play a role in neuroprotection. It also has been demonstrated that argon treatment could mitigate brain damage, reduce excessive microglial activation, and subsequently attenuate brain inflammation. Despite intensive research, the further exact mechanism remains unclear. In this study, human neuroblastoma cells were damaged in vitro with rotenone over a period of 4 hours (to mimic cerebral ischemia and reperfusion damage), followed by a 2-hour post-conditioning with argon (75%). In a separate in vivo experiment, retinal ischemia/reperfusion injury was induced in rats by increasing intraocular pressure for 1 hour. Upon reperfusion, argon was administered by inhalation for 2 hours. Argon reduced the binding of the transcription factors signal transducer and activator of transcription 3, nuclear factor kappa B, activator protein 1, and nuclear factor erythroid 2-related factor 2, which are involved in regulation of neuronal damage. Flow cytometry analysis showed that argon downregulated the Fas ligand. Some transcription factors were regulated by toll-like receptors; therefore, their effects could be eliminated, at least in part, by the TLR2 and TLR4 inhibitor oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC). Argon treatment reduced microglial activation after retinal ischemia/reperfusion injury. Subsequent quantitative polymerase chain reaction analysis revealed a reduction in the pro-inflammatory cytokines interleukin (IL-1α), IL-1β, IL-6, tumor necrosis factor α, and inducible nitric oxide synthase. Our results suggest that argon reduced the extent of inflammation in retinal neurons after ischemia/reperfusion injury by suppression of transcription factors crucial for microglial activation. Argon has no known side effects or narcotic properties; therefore, therapeutic use of this noble gas appears ideal for treatment of patients with neuronal damage in retinal ischemia/reperfusion injury. The animal experiments were approved by the Commission for Animal Care of the University of Freiburg (approval No. 35-9185.81/G14-122) on October 19, 2012.
Published: 2020

32. Carbon Monoxide Exerts Functional Neuroprotection After Cardiac Arrest Using Extracorporeal Resuscitation in Pigs

Author: Nils Schallner, Lorenz Meinel, Ulrich Goebel, Fabian A. Kari, Hartmut Buerkle, Christoph Steiger, Martin A. Schick, Soroush Doostkam, Jakob Wollborn, and Nils Schroeter
Subjects: Male, Resuscitation, Swine, medicine.medical_treatment, Cerebral oxygen saturation, Critical Care and Intensive Care Medicine, Extracorporeal, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, medicine, Animals, Extracorporeal cardiopulmonary resuscitation, Cardiopulmonary resuscitation, Cerebral perfusion pressure, Carbon Monoxide, business.industry, Brain, 030208 emergency & critical care medicine, Cardiopulmonary Resuscitation, Heart Arrest, Transcranial Doppler, Treatment Outcome, 030228 respiratory system, Cerebrovascular Circulation, Anesthesia, Circulatory system, business
Abstract: OBJECTIVES Neurologic damage following cardiac arrest remains a major burden for modern resuscitation medicine. Cardiopulmonary resuscitation with extracorporeal circulatory support holds the potential to reduce morbidity and mortality. Furthermore, the endogenous gasotransmitter carbon monoxide attracts attention in reducing cerebral injury. We hypothesize that extracorporeal resuscitation with additional carbon monoxide application reduces neurologic damage. DESIGN Randomized, controlled animal study. SETTING University research laboratory. SUBJECTS Landrace-hybrid pigs. INTERVENTIONS In a porcine model, carbon monoxide was added using a novel extracorporeal releasing system after resuscitation from cardiac arrest. MEASUREMENTS AND MAIN RESULTS As markers of cerebral function, neuromonitoring modalities (somatosensory-evoked potentials, cerebral oximetry, and transcranial Doppler ultrasound) were used. Histopathologic damage and molecular markers (caspase-3 activity and heme oxygenase-1 expression) were analyzed. Cerebral oximetry showed fast rise in regional oxygen saturation after carbon monoxide treatment at 0.5 hours compared with extracorporeal resuscitation alone (regional cerebral oxygen saturation, 73% ± 3% vs 52% ± 8%; p < 0.05). Median nerve somatosensory-evoked potentials showed improved activity upon carbon monoxide treatment, whereas post-cardiac arrest cerebral perfusion differences were diminished. Histopathologic damage scores were reduced compared with customary resuscitation strategies (hippocampus: sham, 0.4 ± 0.2; cardiopulmonary resuscitation, 1.7 ± 0.4; extracorporeal cardiopulmonary resuscitation, 2.3 ± 0.2; extracorporeal cardiopulmonary resuscitation with carbon monoxide application [CO-E-CPR], 0.9 ± 0.3; p < 0.05). Furthermore, ionized calcium-binding adaptor molecule 1 staining revealed reduced damage patterns upon carbon monoxide treatment. Caspase-3 activity (cardiopulmonary resuscitation, 426 ± 169 pg/mL; extracorporeal cardiopulmonary resuscitation, 240 ± 61 pg/mL; CO-E-CPR, 89 ± 26 pg/mL; p < 0.05) and heme oxygenase-1 (sham, 1 ± 0.1; cardiopulmonary resuscitation, 2.5 ± 0.4; extracorporeal cardiopulmonary resuscitation, 2.4 ± 0.2; CO-E-CPR, 1.4 ± 0.2; p < 0.05) expression were reduced after carbon monoxide exposure. CONCLUSIONS Carbon monoxide application during extracorporeal resuscitation reduces injury patterns in neuromonitoring and decreases histopathologic cerebral damage by reducing apoptosis. This may lay the basis for further clinical translation of this highly salutary substance.
Published: 2020
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33. Inhalative as well as Intravenous Administration of H

Author: Stefanie, Scheid, Max, Goeller, Wolfgang, Baar, Jakob, Wollborn, Hartmut, Buerkle, Günther, Schlunck, Wolf, Lagrèze, Ulrich, Goebel, and Felix, Ulbrich
Subjects: Rats, Sprague-Dawley, Vascular Endothelial Growth Factor A, Ischemia, Reperfusion Injury, Animals, Administration, Intravenous, Hydrogen Sulfide, Neuroprotection, Retina, Rats
Abstract: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (HIschemia-reperfusion injury was induced in rats by a temporary increase in intraocular pressure (1 h). HBoth inhalative and intravenously delivered HHydrogen sulfide acts, at least in part, via the mitogen-activated protein kinase (MAPK) ERK1/2 to reduce apoptosis and inflammation. Both inhalative H
Published: 2022

34. Versteckte lexikographische Information: Möglichkeiten ihrer Erschließung dargestellt am Beispiel des Frühneuhochdeutschen Wörterbuchs

Author: Ulrich Goebel, Ingrid Lemberg, Oskar Reichmann
Published: 2011

35. Extracorporeal resuscitation with carbon monoxide improves renal function by targeting inflammatory pathways in cardiac arrest in pigs

Author: Cornelius Hermann, Christian Wunder, Ulrich Goebel, Bjoern Schlueter, Patric Diel, Martin A. Schick, Johannes Schmidt, Jakob Wollborn, Christoph Steiger, Hartmut Buerkle, and Lorenz Meinel
Subjects: Extracorporeal Circulation, Resuscitation, Swine, Physiology, medicine.medical_treatment, education, Renal function, Apoptosis, 030204 cardiovascular system & hematology, Kidney Function Tests, Extracorporeal, 03 medical and health sciences, 0302 clinical medicine, Lipocalin-2, Animals, Medicine, Cardiopulmonary resuscitation, Inflammation, Carbon Monoxide, business.industry, Acute kidney injury, 030208 emergency & critical care medicine, medicine.disease, Cardiopulmonary Resuscitation, Heart Arrest, Anesthesia, Life support, Successful resuscitation, Kidney Diseases, Inflammatory pathways, business, Biomarkers
Abstract: Deleterious consequences like acute kidney injury frequently occur upon successful resuscitation from cardiac arrest. Extracorporeal life support is increasingly used to overcome high cardiac arrest mortality. Carbon monoxide (CO) is an endogenous gasotransmitter, capable of reducing renal injury. In our study, we hypothesized that addition of CO to extracorporeal resuscitation hampers severity of renal injury in a porcine model of cardiac arrest. Hypoxic cardiac arrest was induced in pigs. Animals were resuscitated using a conventional [cardiopulmonary resuscitation (CPR)], an extracorporeal (E-CPR), or a CO-assisted extracorporeal (CO-E-CPR) protocol. CO was applied using a membrane-controlled releasing system. Markers of renal injury were measured, and histopathological analyses were carried out. We investigated renal pathways involving inflammation as well as apoptotic cell death. No differences in serum neutrophil gelatinase-associated lipocalin (NGAL) were detected after CO treatment compared with Sham animals (Sham 71 ± 7 and CO-E-CPR 95 ± 6 ng/mL), while NGAL was increased in CPR and E-CPR groups (CPR 135 ± 11 and E-CPR 124 ± 5 ng/mL; P < 0.05). Evidence for histopathological damage was abrogated after CO application. CO increased renal heat shock protein 70 expression and reduced inducible cyclooxygenase 2 (CPR: 60 ± 8; E-CPR 56 ± 8; CO-E-CPR 31 ± 3 µg/mL; P < 0.05). Caspase 3 activity was decreased (CPR 1,469 ± 276; E-CPR 1,670 ± 225; CO-E-CPR 755 ± 83 pg/mL; P < 0.05). Furthermore, we found a reduction in renal inflammatory signaling upon CO treatment. Our data demonstrate improved renal function by extracorporeal CO treatment in a porcine model of cardiac arrest. CO reduced proinflammatory and proapoptotic signaling, characterizing beneficial aspects of a novel treatment option to overcome high mortality.
Published: 2019
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36. Intraoperative transfusion practices and perioperative outcome in the European elderly: A secondary analysis of the observational ETPOS study

Author: Grusser L., Keszei A., Coburn M., Rossaint R., Ziemann S., Kowark A, Daniela Filipescu, Sibylle Kozek-Langenecker, Juan V Llau Pitarch, Susan Mallett, Peter Martus, Idit Matot, Jens Meier, Axel Unterrainer, Dieter Adelmann, Daniel von Langen, Petra Innerhofer, Nicole Innerhofer-Pompernigg, Stefan De Hert, Luc De Baerdemaeker, Jurgen van Limmen, Piet Wyffels, Björn Heyse, Margot Vanderlaenen, Maud Beran, David Kahn, Audrey Prospiech, Luc Jamaer, Freya Mulders, Stefan Jacobs, Wannes Baeten, Sofie Platteau, Isabelle Maquoi, Severine Lauwick, Marc Senard, Vincent Ninane, Jean-Pierre Lecoq, Pierre Boveroux, Grégory Hans, Marcel Vercauteren, Brigitte Leva, Benoit Plichon, Vojislav Vujanovič, Ismet Suljevic, Hened Kelle, Denis Gustin, Matea Bogdanovic Dvorscak, Tamara Lupis, Jadranka Pavičić Šarić, Nataša Paklar, Dagmar Oberhofer, Ira Skok, Borana Kirigin, Ikic Visnja, Marina Kresic, Slavica Kvolik, Renatas Krobot, Vladimir Cerny, Jana Striteska, Marcela Bilska, Petr Štourač, Hana Harazim, Olga Smékalová, Martina Kosinová, Jozef Klučka, Rita Pacasová, Kim Ekelund, Indrek Rätsep, Juri Oganjan, Nadezda Smirnova, Peeter Kivik, Juri Karjagin, Alar Rokk, Alar Sõrmus, Bertrand Rozec, Jean-Christophe Rigal, Jean-Pierre Gouraud, Anne-Marie Chupin, Xavier Ambrosi, Laurent Brisard, Sylvie Decagny, Charles Marc Samama, Lionel Lidzborski, Matthieu Boisson, Anne-Laure Arcade, Gilbert Lorre, Peter Rosenberger, Hannah Merz, Ulrich Goebel, Bettina Schnitter, Hartmut Buerkle, Roland Tomasi, Vera von Dossow-Hanfstingl, Florian Brettner, Andreas Bayer, André Gottschalk, Nicolas Jakobs, Mark Coburn, Ana Kowark, Rolf Rossaint, Rita Laufenberg, Marion Ferner, Michael Schuster, Lydia Strys, Susanne Mauff, Kornel Skitek, Ewa Zielinska-Skitek, Gregor Schittek, Andreas Hoeft, Andreas Fleischer, Maria Wittmann, Florian Kessler, Anne Rohner, Peter Kranke, Christian Wunder, Johanna Jokinen, Kristin Budow, Christopher Prasser, Eva Werner, Alina Balandin, Norbert Ahrens, Kai Zacharowski, Patrick Meybohm, Kassiani Theodoraki, George Giokas, Tasoulis Marios-Konstantinos, Ageliki Pandazi, Aikaterini Kyttari, Eygenia Koursoumi, Georgios Anthopoulos, Antonis Andreou, Athanasios Rantis, Dimitrios Valsamidis, Pelagia Klimi, Konstantinos Katsanoulas, Demetrios Korfiotis, Christos Soumelidis, Fotios Papaspyros, Olga Kiskira, Tilemachos Paraskeuopoulos, Donal Buggy, Mortimer Kelleher, Liz Coghlan, Vladimir Verenkin, Anat Cattan, Francesco Bona, Felicino Debernardi, Andrea Cortegiani, Santi Maurizio Raineri, Giuseppe Accurso, Elena Gramigni, Leonardo Cenni, Laura Campiglia, Irene Lorenzi, Maria Grazia Militello, Tamara Biscioni, Andrius Macas, Daiva Apanaviciute, Darius Trepenaitis, Arunas Gelmanas, Diana Bilshiene, Jurate Sipylaite, Gabija Tomkute, Egle Kontrimaviciut, Renatas Tikuisis, Francis Borg, Ion Chesov, Serghei Cobiletchi, Victoria Moghildea, Bas Verdouw, J F van Poorten, Nick van Dasselaar, Marcus Daniel Lance, Britta de Waal, Lucienne Kropman, Peter van Noord, Benedikt Preckel, Lena Koers, Markus W Hollmann, Holger Baumann, Ankie W M M Koopman-van Gemert, Tore Reikvam, Tore Hervig, Kasper Gymoese Berthelsen, Ingvild Hausberg Sørvoll, Mirosław Czuczwar, Michał Borys, Paweł Piwowarczyk, Suzana Parente, Diogo Martins, Gloria Tareco, Ligia Reis, Joana Amaral, Daniel Ferreira, José Manuel Gonçalves Aguiar, Zélia Moreira, Filipa Lagarto, Filipa Pereira, Maria Lina Miranda, Sofia Serra, Alexandre Carrilho, José Pinto, Sandra Dias, Rita Poeria, Filipe Linda, Silvia Pica, Helder Martinho, Francisco Matias, Claudia Alves, Valentina Almeida, Margarida Marques, Emilia Martires, Piedade Gomes, Elizabete Pereira, Joana Jesus, Claudia Carreira, Carlos Seco, Carlos Bento, Helena Vieira, Luciane Pereira, Fernando Pinto, Luisa Silva, Marta Azenha, Maged Zarif, Ana Bernardino, Ana Raimundo, Ana Lopes, Melissa Fernandes, Beatriz Campos, Ana Macedo, Filipe Pinheiro, Sonia Duarte, Alexandra Saraiva, Catia Real, Marilena Alina Paunescu, Alexandru Bogdan Prodan, Mihai Stefan, Cristian Boros, Marius Tifrea, Anca Dragan, Horhota Lucian, Alida Moise, Carmen Arion-Balescu, Natalia Mincu, Viorel Gherghina, Iulia Cindea, Dan Costea, Ravzan Popescu, Dana Tomescu, Ecaterina Scarlatescu, Esenia Calancea, Ruxandra Copotoiu, Sanda Maria Copotoiu, Victoria Barsan, Dan Corneci, Rely Manolescu, Toma Diana, Denisa Nitu, Georgian Popica, Gabriela Droc, Nicoleta Jipa Lavina, Roxana Ciobanasu, Anna Maria Munteanu, Denisa Anastase, Iona Grintescu, Liliana Mirea, Alexandra Manoleli, Ciobanu Elena, Mary Nicoleta Lupu, Madalina Nina Sandu, Bicolae Bacalbasa, Florenta Calarasu, Alexey Grytsan, Andrey Gasenkampf, Alexander Kulikov, Alexander Shmigelsky, Vojislava Nescovic, Rade Vukovic, Uros Petrovic, Milic Veljovic, Dragana Unic-Stojanovic, Gordana Jovanovic, Ivana Kvrgic, Dragana Rakic, Roman Záhorec, Daniel Cintula, Tomas Veselovsky, Katarina Galkova, Jordana Stevikova, Andrea Číková, Zora Flassikova, Anna Dobisova, Jasmina Markovic Bozic, Minca Voje, Andriy Grynyuk, Alenka Spindler Yesel, Sabina Stivan, Peter Poredos, Darja Kasnik, Jasna Uranjek, Raquel Ferrandis, Sofia Machado, Liliana Henao, Tania Moreno, Ana Izquierdo, Carlos Delgado, Angela Camps, Susana Manrique, Alejandro Arbelaez, Pilar Tormos, Helena Serrano, Irene Garcia, Elvira Bisbe Vives, Luís Moltó, Tania Villar, Enrique Moret, Raquel Tolós, Esther Martínez, Misericordia Basora, Beatriz Tena, Roger Pujol, Jorge Vera Bella, Thomas Mallor, Pablo Mondero, Luis Lopez, Francisco Hidalgo, Maria Bermudez Lopez, Ana Velasco, Begona Bascuas, Victoria Moral, Diana Gómez Martinez, Alfredo Merten, J A Fernández, Nadia Diana Kinast, A Font, Maggi Genaro, Emilia Guasch, Fernando Gilsanz, Raul Martinez, Renato Schiraldi, Ever Martinez, Marta Barquero López, Alexo Lopez Alvarez, Yvan Enrique Sanchez Sanchez, Adriana Roman Fernandez, Olalla Varela Garcia, Marian Angeles Orallo Moran, Veronica Gonzalez Monzon, Óscar Sánchez López, David Sanchez Perez, Pablo Molano Diaz, Concepcion Cassinello, Maria Pilar Jubera, Maria Soler Pedrola, Julio Belmonte Cuenca, Sören Söndergaard, Till Rudolph, Kristin Åkeröy, Monir Jawad, Yousif Saeed, Sergej Safonov, Mona Andersson, Jan Wernerman, Suzanne Odeberg-Wernerman, Tommi Blom, Nesil Deger Coskunfirat, Zekiye Bigat, Suat Sanlı, O Koray Coskunfirat, Atilla Ramazanoğlu, Neval Boztug Uz, Ali Emre Camci, Omur Aksoy, Esra Saka, Oguzhan Arun, Sevda Ozkardesler, Dilek Omur, Mert Akan, Zuleyha Kazak Bengisun, Hakan Yılmaz, Perihan Ekmekci, Onur Selvi, Neslihan Alkis, Çiğdem Yıldırım, Başak Ceyda Meço, Zekeriyye Alanoğlu, Sergiy Vorotyntsev, Yevgen Yakymenko, Galina Troyan, Mohammed Alousi, Sarah James, Paula Meale, Ahmed Chishti, Matt Garner, Rita Singh, Nicola Hirschauer, Charley Higham, Andrea Bell, Alistair Cain, Chris Perry, Katy Davies, Claire Leech, Verity Calder, Shaman Jhanji, Varma Sandeep, Karen Simeson, Philip Watt, Nigel Dunk, Rosemary Ferrie, Margaret Wright, Lynn Everett, Andrew Ferguson, Laura Espie, Gail Browne, Matthew 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F., van Dasselaar, Nick, Lance, Marcus Daniel, de Waal, Britta, Kropman, Lucienne, van Noord, Peter, Preckel, Benedikt, Koers, Lena, Hollmann, Markus W., Baumann, Holger, De Hert, Stefan, Koopman-van Gemert, Ankie W. M. 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A., Kinast, Nadia Diana, Font, A., Genaro, Maggi, Guasch, Emilia, Gilsanz, Fernando, Martinez, Raul, Schiraldi, Renato, Senard, Marc, Martinez, Ever, Barquero López, Marta, Lopez Alvarez, Alexo, Sanchez Sanchez, Yvan Enrique, Roman Fernandez, Adriana, Varela Garcia, Olalla, Orallo Moran, Marian Angeles, Gonzalez Monzon, Veronica, Sánchez López, Óscar, Sanchez Perez, David, Ninane, Vincent, Molano Diaz, Pablo, Cassinello, Concepcion, Pilar Jubera, Maria, Soler Pedrola, Maria, Belmonte Cuenca, Julio, Söndergaard, Sören, Rudolph, Till, Åkeröy, Kristin, Jawad, Monir, Saeed, Yousif, Lecoq, Jean-Pierre, Safonov, Sergej, Andersson, Mona, Wernerman, Jan, Odeberg-Wernerman, Suzanne, Blom, Tommi, Deger Coskunfirat, Nesil, Bigat, Zekiye, Sanlı, Suat, Coskunfirat, O. Koray, Ramazanoğlu, Atilla, Boveroux, Pierre, Boztug Uz, Neval, Camci, Ali Emre, Aksoy, Omur, Saka, Esra, Arun, Oguzhan, Ozkardesler, Sevda, Omur, Dilek, Akan, Mert, Bengisun, Zuleyha Kazak, Yılmaz, Hakan, Hans, Grégory, Ekmekci, Perihan, Selvi, Onur, Alkis, Neslihan, Yıldırım, Çiğdem, Ceyda Meço, Başak, Alanoğlu, Zekeriyye, Vorotyntsev, Sergiy, Yakymenko, Yevgen, Troyan, Galina, Alousi, Mohammed, Vercauteren, Marcel, James, Sarah, Meale, Paula, Chishti, Ahmed, Garner, Matt, Singh, Rita, Hirschauer, Nicola, Higham, Charley, Bell, Andrea, Cain, Alistair, Perry, Chris, Leva, Brigitte, Davies, Katy, Leech, Claire, Calder, Verity, Jhanji, Shaman, Sandeep, Varma, Simeson, Karen, Watt, Philip, Dunk, Nigel, Ferrie, Rosemary, Wright, Margaret, Plichon, Benoit, Everett, Lynn, Ferguson, Andrew, Espie, Laura, Browne, Gail, Dickinson, Matthew, Nair, Ashok, Clements, Deborah, Carvalho, Peter, Collyer, Thomas, Bolten, Jens, Vujanovič, Vojislav, Zsisku, Lajos, Petri, Attila, Ramadan, Mohammed, Ellimah, Tracey, Suljevic, Ismet, Kelle, Hened, Gustin, Denis, Bogdanovic Dvorscak, Matea, Lupis, Tamara, Pavičić Šarić, Jadranka, Paklar, Nataša, Oberhofer, Dagmar, Skok, Ira, Kirigin, Borana, Visnja, Ikic, Kresic, Marina, Kvolik, Slavica, Krobot, Renatas, Cerny, Vladimir, Striteska, Jana, Bilska, Marcela, Filipescu, Daniela, Štourač, Petr, Harazim, Hana, Smékalová, Olga, Kosinová, Martina, Klučka, Jozef, Pacasová, Rita, Ekelund, Kim, Rätsep, Indrek, Oganjan, Juri, Smirnova, Nadezda, Kozek-Langenecker, Sibylle, Kivik, Peeter, Karjagin, Juri, Rokk, Alar, Sõrmus, Alar, Rozec, Bertrand, Rigal, Jean-Christophe, Gouraud, Jean-Pierre, Chupin, Anne-Marie, Ambrosi, Xavier, Brisard, Laurent, Llau Pitarch, Juan V., Decagny, Sylvie, Samama, Charles Marc, Lidzborski, Lionel, Boisson, Matthieu, Arcade, Anne-Laure, Lorre, Gilbert, Rosenberger, Peter, Merz, Hannah, Goebel, Ulrich, Schnitter, Bettina, Mallett, Susan, Buerkle, Hartmut, Tomasi, Roland, von Dossow-Hanfstingl, Vera, Brettner, Florian, Bayer, Andreas, Gottschalk, André, Jakobs, Nicolas, Coburn, Mark, Kowark, Ana, Rossaint, Rolf, Grusser L., Keszei A., Coburn M., Rossaint R., Ziemann S., Kowark A, Daniela Filipescu, Sibylle Kozek-Langenecker, Juan V Llau Pitarch, Susan Mallett, Peter Martus, Idit Matot, Jens Meier, Axel Unterrainer, Dieter Adelmann, Daniel von Langen, Petra Innerhofer, Nicole Innerhofer-Pompernigg, Stefan De Hert, Luc De Baerdemaeker, Jurgen van Limmen, Piet Wyffels, Björn Heyse, Margot Vanderlaenen, Maud Beran, David Kahn, Audrey Prospiech, Luc Jamaer, Freya Mulders, Stefan Jacobs, Wannes Baeten, Sofie Platteau, Isabelle Maquoi, Severine Lauwick, Marc Senard, Vincent Ninane, Jean-Pierre Lecoq, Pierre Boveroux, Grégory Hans, Marcel Vercauteren, Brigitte Leva, Benoit Plichon, Vojislav Vujanovič, Ismet Suljevic, Hened Kelle, Denis Gustin, Matea Bogdanovic Dvorscak, Tamara Lupis, Jadranka Pavičić Šarić, Nataša Paklar, Dagmar Oberhofer, Ira Skok, Borana Kirigin, Ikic Visnja, Marina Kresic, Slavica Kvolik, Renatas Krobot, Vladimir Cerny, Jana Striteska, Marcela Bilska, Petr Štourač, Hana Harazim, Olga Smékalová, Martina Kosinová, Jozef Klučka, Rita Pacasová, Kim Ekelund, Indrek Rätsep, Juri Oganjan, Nadezda Smirnova, Peeter Kivik, Juri Karjagin, Alar Rokk, Alar Sõrmus, Bertrand Rozec, Jean-Christophe Rigal, Jean-Pierre Gouraud, Anne-Marie Chupin, Xavier Ambrosi, Laurent Brisard, Sylvie Decagny, Charles Marc Samama, Lionel Lidzborski, Matthieu Boisson, Anne-Laure Arcade, Gilbert Lorre, Peter Rosenberger, Hannah Merz, Ulrich Goebel, Bettina Schnitter, Hartmut Buerkle, Roland Tomasi, Vera von Dossow-Hanfstingl, Florian Brettner, Andreas Bayer, André Gottschalk, Nicolas Jakobs, Mark Coburn, Ana Kowark, Rolf Rossaint, Rita Laufenberg, Marion Ferner, Michael Schuster, Lydia Strys, Susanne Mauff, Kornel Skitek, Ewa Zielinska-Skitek, Gregor Schittek, Andreas Hoeft, Andreas Fleischer, Maria Wittmann, Florian Kessler, Anne Rohner, Peter Kranke, Christian Wunder, Johanna Jokinen, Kristin Budow, Christopher Prasser, Eva Werner, Alina Balandin, Norbert Ahrens, Kai Zacharowski, Patrick Meybohm, Kassiani Theodoraki, George Giokas, Tasoulis Marios-Konstantinos, Ageliki Pandazi, Aikaterini Kyttari, Eygenia Koursoumi, Georgios Anthopoulos, Antonis Andreou, Athanasios Rantis, Dimitrios Valsamidis, Pelagia Klimi, Konstantinos Katsanoulas, Demetrios Korfiotis, Christos Soumelidis, Fotios Papaspyros, Olga Kiskira, Tilemachos Paraskeuopoulos, Donal Buggy, Mortimer Kelleher, Liz Coghlan, Vladimir Verenkin, Anat Cattan, Francesco Bona, Felicino Debernardi, Andrea Cortegiani, Santi Maurizio Raineri, Giuseppe Accurso, Elena Gramigni, Leonardo Cenni, Laura Campiglia, Irene Lorenzi, Maria Grazia Militello, Tamara Biscioni, Andrius Macas, Daiva Apanaviciute, Darius Trepenaitis, Arunas Gelmanas, Diana Bilshiene, Jurate Sipylaite, Gabija Tomkute, Egle Kontrimaviciut, Renatas Tikuisis, Francis Borg, Ion Chesov, Serghei Cobiletchi, Victoria Moghildea, Bas Verdouw, J F van Poorten, Nick van Dasselaar, Marcus Daniel Lance, Britta de Waal, Lucienne Kropman, Peter van Noord, Benedikt Preckel, Lena Koers, Markus W Hollmann, Holger Baumann, Ankie W M M Koopman-van Gemert, Tore Reikvam, Tore Hervig, Kasper Gymoese Berthelsen, Ingvild Hausberg Sørvoll, Mirosław Czuczwar, Michał Borys, Paweł Piwowarczyk, Suzana Parente, Diogo Martins, Gloria Tareco, Ligia Reis, Joana Amaral, Daniel Ferreira, José Manuel Gonçalves Aguiar, Zélia Moreira, Filipa Lagarto, Filipa Pereira, Maria Lina Miranda, Sofia Serra, Alexandre Carrilho, José Pinto, Sandra Dias, Rita Poeria, Filipe Linda, Silvia Pica, Helder Martinho, Francisco Matias, Claudia Alves, Valentina Almeida, Margarida Marques, Emilia Martires, Piedade Gomes, Elizabete Pereira, Joana Jesus, Claudia Carreira, Carlos Seco, Carlos Bento, Helena Vieira, Luciane Pereira, Fernando Pinto, Luisa Silva, Marta Azenha, Maged Zarif, Ana Bernardino, Ana Raimundo, Ana Lopes, Melissa Fernandes, Beatriz Campos, Ana Macedo, Filipe Pinheiro, Sonia Duarte, Alexandra Saraiva, Catia Real, Marilena Alina Paunescu, Alexandru Bogdan Prodan, Mihai Stefan, Cristian Boros, Marius Tifrea, Anca Dragan, Horhota Lucian, Alida Moise, Carmen Arion-Balescu, Natalia Mincu, Viorel Gherghina, Iulia Cindea, Dan Costea, Ravzan Popescu, Dana Tomescu, Ecaterina Scarlatescu, Esenia Calancea, Ruxandra Copotoiu, Sanda Maria Copotoiu, Victoria Barsan, Dan Corneci, Rely Manolescu, Toma Diana, Denisa Nitu, Georgian Popica, Gabriela Droc, Nicoleta Jipa Lavina, Roxana Ciobanasu, Anna Maria Munteanu, Denisa Anastase, Iona Grintescu, Liliana Mirea, Alexandra Manoleli, Ciobanu Elena, Mary Nicoleta Lupu, Madalina Nina Sandu, Bicolae Bacalbasa, Florenta Calarasu, Alexey Grytsan, Andrey Gasenkampf, Alexander Kulikov, Alexander Shmigelsky, Vojislava Nescovic, Rade Vukovic, Uros Petrovic, Milic Veljovic, Dragana Unic-Stojanovic, Gordana Jovanovic, Ivana Kvrgic, Dragana Rakic, Roman Záhorec, Daniel Cintula, Tomas Veselovsky, Katarina Galkova, Jordana Stevikova, Andrea Číková, Zora Flassikova, Anna Dobisova, Jasmina Markovic Bozic, Minca Voje, Andriy Grynyuk, Alenka Spindler Yesel, Sabina Stivan, Peter Poredos, Darja Kasnik, Jasna Uranjek, Raquel Ferrandis, Sofia Machado, Liliana Henao, Tania Moreno, Ana Izquierdo, Carlos Delgado, Angela Camps, Susana Manrique, Alejandro Arbelaez, Pilar Tormos, Helena Serrano, Irene Garcia, Elvira Bisbe Vives, Luís Moltó, Tania Villar, Enrique Moret, Raquel Tolós, Esther Martínez, Misericordia Basora, Beatriz Tena, Roger Pujol, Jorge Vera Bella, Thomas Mallor, Pablo Mondero, Luis Lopez, Francisco Hidalgo, Maria Bermudez Lopez, Ana Velasco, Begona Bascuas, Victoria Moral, Diana Gómez Martinez, Alfredo Merten, J A Fernández, Nadia Diana Kinast, A Font, Maggi Genaro, Emilia Guasch, Fernando Gilsanz, Raul Martinez, Renato Schiraldi, Ever Martinez, Marta Barquero López, Alexo Lopez Alvarez, Yvan Enrique Sanchez Sanchez, Adriana Roman Fernandez, Olalla Varela Garcia, Marian Angeles Orallo Moran, Veronica Gonzalez Monzon, Óscar Sánchez López, David Sanchez Perez, Pablo Molano Diaz, Concepcion Cassinello, Maria Pilar Jubera, Maria Soler Pedrola, Julio Belmonte Cuenca, Sören Söndergaard, Till Rudolph, Kristin Åkeröy, Monir Jawad, Yousif Saeed, Sergej Safonov, Mona Andersson, Jan Wernerman, Suzanne Odeberg-Wernerman, Tommi Blom, Nesil Deger Coskunfirat, Zekiye Bigat, Suat Sanlı, O Koray Coskunfirat, Atilla Ramazanoğlu, Neval Boztug Uz, Ali Emre Camci, Omur Aksoy, Esra Saka, Oguzhan Arun, Sevda Ozkardesler, Dilek Omur, Mert Akan, Zuleyha Kazak Bengisun, Hakan Yılmaz, Perihan Ekmekci, Onur Selvi, Neslihan Alkis, Çiğdem Yıldırım, Başak Ceyda Meço, Zekeriyye Alanoğlu, Sergiy Vorotyntsev, Yevgen Yakymenko, Galina Troyan, Mohammed Alousi, Sarah James, Paula Meale, Ahmed Chishti, Matt Garner, Rita Singh, Nicola Hirschauer, Charley Higham, Andrea Bell, Alistair Cain, Chris Perry, Katy Davies, Claire Leech, Verity Calder, Shaman Jhanji, Varma Sandeep, Karen Simeson, Philip Watt, Nigel Dunk, Rosemary Ferrie, Margaret Wright, Lynn Everett, Andrew Ferguson, Laura Espie, Gail Browne, Matthew Dickinson, Ashok Nair, Deborah Clements, Peter Carvalho, Thomas Collyer, Jens Bolten, Lajos Zsisku, Attila Petri, Mohammed Ramadan, Tracey Ellimah, Anesthesiology, ACS - Diabetes & metabolism, APH - Quality of Care, ACS - Heart failure & arrhythmias, APH - Global Health, and ACS - Microcirculation
Subjects: Clinical Oncology, Male, Science, Clinical Decision-Making, Cancer Treatment, Surgical and Invasive Medical Procedures, Geographical Locations, Diagnostic Medicine, Outcome Assessment, Health Care, Medicine and Health Sciences, Humans, Blood Transfusion, Prospective Studies, Aged, Aged, 80 and over, Intraoperative Care, Multidisciplinary, Transfusion Medicine, Anemia, Hematology, Clinical Laboratory Sciences, Health Care, Europe, Surgical Oncology, Oncology, Age Groups, Elective Surgical Procedures, People and Places, Medicine, Population Groupings, Female, Geriatric Care, Clinical Medicine, Erythrocyte Transfusion, Research Article
Abstract: PLOS ONE 17(1), e0262110 (2022). doi:10.1371/journal.pone.0262110, Published by PLOS, San Francisco, California, US
Published: 2022
Full Text: View/download PDF

37. Hydrogen Sulfide Reduces Ischemia and Reperfusion Injury in Neuronal Cells in a Dose- and Time-Dependent Manner

Author: Stefanie Scheid, Max Goeller, Wolfgang Baar, Jakob Wollborn, Hartmut Buerkle, Günther Schlunck, Wolf Lagrèze, Ulrich Goebel, and Felix Ulbrich
Subjects: Male, Time Factors, QH301-705.5, ischemia–reperfusion injury, hydrogen sulfide, Apoptosis, Drug Administration Schedule, Retina, Article, Rats, Sprague-Dawley, H2S, Animals, Biology (General), Phosphorylation, QD1-999, Inflammation, Neurons, Dose-Response Relationship, Drug, NF-kappa B, equipment and supplies, Rats, Chemistry, Neuroprotective Agents, retinal ganglion cells, NADPH Oxidase 4, Reperfusion Injury, Cytokines, neuroprotection
Abstract: Background: The ischemia-reperfusion injury (IRI) of neuronal tissue, such as the brain and retina, leads to possible cell death and loss of function. Current treatment options are limited, but preliminary observations suggest a protective effect of hydrogen sulfide (H2S). However, the dosage, timing, and mechanism of inhaled H2S treatment after IRI requires further exploration. Methods: We investigated possible neuroprotective effects of inhaled H2S by inducing retinal ischemia–reperfusion injury in rats for the duration of 1 h (120 mmHg), followed by the administration of hydrogen sulfide (H2S) for 1 h at different time points (0, 1.5, and 3 h after the initiation of reperfusion) and at different H2S concentrations (120, 80, and 40 ppm). We quantified the H2S effect by conducting retinal ganglion cell counts in fluorogold-labeled animals 7 days after IRI. The retinal tissue was harvested after 24 h for molecular analysis, including qPCR and Western blotting. Apoptotic and inflammatory mediators, transcription factors, and markers for oxidative stress were investigated. Histological analyses of the retina and the detection of inflammatory cytokines in serum assays were also performed. Results: The effects of inhaled H2S were most evident at a concentration of 80 ppm administered 1.5 h after IRI. H2S treatment increased the expression of anti-apoptotic Bcl-2, decreased pro-apoptotic Bax expression, reduced the release of the inflammatory cytokines IL-1β and TNF-α, attenuated NF-κB p65, and enhanced Akt phosphorylation. H2S also downregulated NOX4 and cystathionine β-synthase. Histological analyses illustrated a reduction in TNF-α in retinal ganglion cells and lower serum levels of TNF-α in H2S-treated animals after IRI. Conclusion: After neuronal IRI, H2S mediates neuroprotection in a time- and dose-dependent manner. The H2S treatment modulated transcription factor NF-κB activation and reduced retinal inflammation.
Published: 2021
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38. st – unmerksam

Author: Ulrich Goebel, Anja Lobenstein-Reichmann, Oskar Reichmann, Ulrich Goebel, Anja Lobenstein-Reichmann, and Oskar Reichmann
Abstract: Das Frühneuhochdeutsche Wörterbuch ist ein alphabetisch geordnetes Bedeutungswörterbuch der Varietäten des Hochdeutschen des 14. bis 17. Jahrhunderts.
Published: 2024

39. quackeln – schlaufe

Author: Ulrich Goebel, Anja Lobenstein-Reichmann, Oskar Reichmann, Ulrich Goebel, Anja Lobenstein-Reichmann, and Oskar Reichmann
Abstract: Das Frühneuhochdeutsche Wörterbuch ist ein alphabetisch geordnetes Bedeutungswörterbuch der Varietäten des Hochdeutschen des 14. bis 17. Jahrhunderts.
Published: 2023

40. A brief history of carbon monoxide and its therapeutic origins

Author: Ulrich Goebel, Christopher P. Hopper, Paige N. Zambrana, and Jakob Wollborn
Subjects: 0301 basic medicine, Cancer Research, Carbon Monoxide, History, Physiology, Clinical Biochemistry, Environmental ethics, Context (language use), History, 19th Century, 030204 cardiovascular system & hematology, History, 20th Century, History, 18th Century, Biochemistry, History, 21st Century, History, Medieval, History, 17th Century, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, History, 16th Century, Animals, Humans, History, Ancient, History, 15th Century
Abstract: It is estimated that 10% of carbon throughout the cosmos is in the form of carbon monoxide (CO). Earth's earliest prebiotic atmosphere included the trinity of gasotransmitters CO, nitric oxide (NO), and hydrogen sulfide (H2S), for which all of life has co-evolved with. The history of CO can be loosely traced to mythological and prehistoric origins with rudimentary understanding emerging in the middle ages. Ancient literature is focused on CO's deadly toxicity which is understandable in the context of our primitive relationship with coal and fire. Scientific inquiry into CO appears to have emerged throughout the 1700s followed by chemical and toxicological profiling throughout the 1800s. Despite CO's ghastly reputation, several of the 18th and 19th century scientists suggested a therapeutic application of CO. Since 2000, the fundamental understanding of CO as a deadly nuisance has undergone a paradigm shift such that CO is now recognized as a neurotransmitter and viable pharmaceutical candidate. This review is intended to provide a brief history on the trace origins pertaining to endogenous formation and therapeutic application of CO.
Published: 2020

41. Carbon monoxide improves haemodynamics during extracorporeal resuscitation in pigs

Author: Martin A. Schick, Lorenz Meinel, Christian Wunder, Eva Ruetten, Hartmut Buerkle, Christoph Steiger, Ulrich Goebel, Jakob Wollborn, Fabian A. Kari, and Christoph Benk
Subjects: Cardiac function curve, Resuscitation, medicine.medical_specialty, Time Factors, Heart disease, Physiology, medicine.medical_treatment, Sus scrofa, education, 030204 cardiovascular system & hematology, Ventricular Function, Left, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, health services administration, Physiology (medical), Internal medicine, medicine, Alarmins, Animals, Myocytes, Cardiac, cardiovascular diseases, Cardiopulmonary resuscitation, health care economics and organizations, Carbon Monoxide, Ejection fraction, business.industry, Microcirculation, Extracorporeal circulation, Hemodynamics, Mouth Mucosa, 030208 emergency & critical care medicine, Recovery of Function, medicine.disease, Cardiopulmonary Resuscitation, Heart Arrest, Cardiovascular physiology, Disease Models, Animal, Shock (circulatory), Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, therapeutics, Signal Transduction
Abstract: Aims Heart disease of different aetiology remains the leading cause of cardiac arrest (CA). Despite efforts to improve the quality of cardiopulmonary resuscitation (CPR), subsequent myocardial and systemic damage after CA still present a major long-term burden. Low-dose carbon monoxide (CO) is known to exert protective effects in cardiovascular pathophysiology but clinical applications are challenged by unfavourable delivery modes. We tested the hypothesis that extracorporeal resuscitation (E-CPR) in combination with controlled fast onset CO delivery results in improved cardiac physiology and haemodynamics. Damage-associated molecular pattern (DAMP) signalling may be part of the molecular mechanism. Methods and results In an established porcine model, E-CPR was performed. While E-CPR leads to similar results as compared to a conventional CPR strategy, CO delivery in combination with E-CPR demonstrated significant cardioprotection. Cardiac performance analysis using echocardiography and thermodilution techniques showed a CO-dependent improved cardiac function compared to severe myocardial dysfunction in CPR and E-CPR (left ventricular ejection fraction: Sham 49 ± 5; CPR 26 ± 2; E-CPR 25 ± 2; CO-E-CPR 31 ± 4; P Conclusions CO treatment restores myocardial function and improves systemic macro- and microhaemodynamics in E-CPR through a reduction in DAMPs.
Published: 2019
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42. Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans

Author: Annika Heuer, Abraham Hulst, NTIRENGANYA Faustin, Giacomo Monti, Stephen Choi, Edward J Caruana, Kresimir Oremus, Kathryn Haigh, Amanda Koh, Denis Protsenko, Ana Maria Minaya Bravo, Abegail Salvana, Mahdad Noursadeghi, Rhiannon Harries, Ayyaz Hussain, Sathish Muthu, Professor T E Madiba, Jie Wu, Maria Wittmann, Donaldo S Arteta-Arteta, Mona Momeni, Mary T. Nabukenya, Birender Balain, Irina Paziuk, Matthew Chan, TRIANTAFYLLIA KOUKOUBANI, Gabrielle Van Ramshorst, Gianluca Pellino, Haya Deeb, Daniele Sances, Salomone Di Saverio, Fernando Cordera, Olufemi Bankole, Patrice Forget, Chu Yik Tang, Daniel Conway, Alejandro Suarez de la Rica, E. Christiaan Boerma, Dion Morton, John Edwards, Markus W. Löffler, ANASTASIA SPARTINOU, Daiana Taddeo, VIKAS KAURA, David Choi, Akbar Vohra, Francesco Della Corte, Alexander Durst, Sebastian Tranca, Samuel Ford, Rajkumar Rajendram, Christina Bali, Bosede Afolabi, Nicola Petrucci, Anne Godier, Dmitri Nepogodiev, Rocco D'andrea, Dana Tomescu, Hans Lederhuber, LAURA GAVRIL, Chetan Khatri, Gabriela Droc, Rupert Pearse, Janet Martin, Ari Ercole, Ibironke Desalu, Dejan Radenkovic, Luis Martin-Villen, Alvaro Rea-Neto, Pablo Monedero, Thomas Pinkney, Stuart White, Antonino Spinelli, Manu Malbrain, Bisola Onajin-Obembe, Tom Lawton, Goran Tulic, R. Arthur Bouwman, Shaktiman Singh, Keith Couper, Benedikt Preckel, Osaid Alser, Isabel Gracia, Daniel Cox, Oumaima Outani, Luís Bento, Stephen Webb, Marzida Mansor, Florent Wallet, Konstantinos Stamatiou, Adesoji Ademuyiwa, Bodil Steen Rasmussen, James Glasbey, Nelson Barros, Adewale Adisa, Olanrewaju Akanmu, Ryckie Wade, Joana Berger-Estilita, Stefano Turi, Sigita Kazune, Ewen Harrison, Mihai Stefan, ANTHONY ADENEKAN, Dhruva Ghosh, Sohini Chakrabortee, Mary Venn, Irène Santos, Michael Sander, Vincent Minville, Francisco Javier Redondo Calvo, Naomi Wright, Ismaïl LAWANI, James Haddow, Axel R. Heller, Anders Oldner, Cesar Aldecoa, Savino Spadaro, Robert Parker, Jibril Bello, Tamas Szakmany, Dhruv Parekh, Alberto ZANGRILLO, LUC HUYGHENS, Beatriz Tena, Tom Abbott, Richard Wilkin, Ulrich Goebel, Anca Irina Ristescu, RODRIGO POVES ALVAREZ, Carlos Silva Faria, Hidde M Kroon, José Azevedo, Herman Lule, Orestis Ioannidis, Sandra Jumbe, Peter Hutchinson, Ayaz Ali, Caroline Holaubek, Luke Hopkins, Kirsten Moller, Morten Bestle, Patricia Alfaro de la Torre, Hyla-Louise Kluyts, Evgeny Grigoryev, Shaman Jhanji, Timothy Cook, Carolina Soledad Romero Garcia, Wolfgang Buhre, Denny Levett, Stefan De Hert, Bianchin Andrea, Monir Jawad, Nicoletta Fossati, Matthias Unterberg, Gianluca Castellani, Oliver Warren, Simon Burg, Jose Trenado Álvarez, Franco Ruberto, Adeline Rankin, Arash Afshari, Gerald Ekwen, Helena Barrasa, Andrew Schache, Carlos Ferrando, Johannes Doerner, Hwei Jene Ng, Ruth Blanco-Colino, Sean Ezekiel Seow, Artigas Antonio, Pablo Lozano Lominchar, Dennis Mazingi, Giovanni LANDONI, Martin Hübner, Weng Ken Chan, Hassan Mashbari, Milagros Niquen-Jimenez, Timothy Short, Mikhail Kirov, Alexander Kulikov, Abdulmueti Alhadi, Frederick Van der Merwe, Mahmoud ElFiky, Kai Henrik Wiborg Lange, Gaetano Gallo, Gustavo Mendonça Ataíde Gomes, Aneel Bhangu, Ioana Grigoras, Carlos Serón, Siobhan McKay, Ruth A Benson, Xavier Borrat, Markus Hollmann, Juan José Segura-Sampedro, Devnandan Chatterjee, and Birgitte Brandsborg
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, General surgery, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Case mix index, Surgical recovery, Pandemic, medicine, Elective surgery, Elective Surgical Procedure, business, Elective caesarean, health care economics and organizations, Predictive modelling
Abstract: Background: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. Methods: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. Results: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. Conclusion: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.
Published: 2020
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43. Early Postoperative Use of Diuretics After Kidney Transplantation Showed Increase in Delayed Graft Function

Author: Kai B. Kaufmann, Wolfgang Baar, Bernd Jaenigen, Julian Knoerlein, Ulrich Goebel, Johannes Kalbhenn, Sebastian Heinrich, Kai Silbach, and Przemyslaw Pisarski
Subjects: Male, medicine.medical_specialty, Acute Renal Injury, 030232 urology & nephrology, Delayed Graft Function, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Furosemide, Germany, medicine, Humans, Mannitol, Postoperative Period, Diuretics, Kidney transplantation, Retrospective Studies, Transplantation, business.industry, Incidence, Middle Aged, medicine.disease, Kidney Transplantation, Surgery, Regression Analysis, Female, business
Abstract: Purpose: In acute renal injury, diuretics are widely considered to be harmful. Nevertheless, they are used frequently after kidney transplantation. We hypothesized that diuretics administered in the early postoperative treatment after kidney transplantation increase the incidence of delayed graft function (DGF). Methods: In this monocentric, retrospective cohort analysis, we screened the closed files of all consecutive patients who underwent kidney transplantation from 2011 to 2017. The outcome variable was DGF, defined as at least 1 hemodialysis within 7 days postoperatively. To stratify for baseline characteristics such as waiting time or cold ischemic period, we employed a propensity score-matched analysis. Further statistical processing included basic descriptive statistics, Mann-Whitney U test, and binary logistic regression analysis. Results: The unmatched cohort included 445 patients and showed a significantly increased rate of DGF for patients who received either furosemide or mannitol or a combination of both (5% vs 25%; P < .001). Mannitol (odds ratio [OR]: 4.094) and furosemide (OR: 2.915) showed a significant correlation with DGF in the multivariate regression analysis. Propensity score-based matching resulted in a matched cohort of 214 patients with balanced baseline risk variables. In this matched cohort, the rate of DGF was significantly increased in patients who received diuretics in the early postoperative treatment (7% vs 16%; P = .031). Conclusion: Our results show that postoperatively administered diuretics are associated with an increased rate of DGF even in a cohort with balanced preoperative risk variables. This study supports recently published reviews, which call diuretics in the transplantation process into question.
Published: 2020

44. Standardized model of porcine resuscitation using a custom-made resuscitation board results in optimal hemodynamic management

Author: J Haberstroh, Jakob Wollborn, Martin A. Schick, Ulrich Goebel, Bjoern Schlueter, and Eva Ruetten
Subjects: medicine.medical_specialty, Resuscitation, Swine, medicine.medical_treatment, Hemodynamics, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Intravascular volume status, Animals, Humans, Medicine, Arterial Pressure, Cardiopulmonary resuscitation, business.industry, Advanced cardiac life support, 030208 emergency & critical care medicine, General Medicine, Stroke volume, Cardiopulmonary Resuscitation, Heart Arrest, Disease Models, Animal, Blood pressure, Emergency Medicine, Cardiology, Arterial blood, Blood Gas Analysis, business
Abstract: Aim Standardized modeling of cardiac arrest and cardiopulmonary resuscitation (CPR) is crucial to evaluate new treatment options. Experimental porcine models are ideal, closely mimicking human-like physiology. However, anteroposterior chest diameter differs significantly, being larger in pigs and thus poses a challenge to achieve adequate perfusion pressures and consequently hemodynamics during CPR, which are commonly achieved during human resuscitation. The aim was to prove that standardized resuscitation is feasible and renders adequate hemodynamics and perfusion in pigs, using a specifically designed resuscitation board for a pneumatic chest compression device. Methods and results A “porcine-fit” resuscitation board was designed for our experiments to optimally use a pneumatic compression device (LUCAS® II, Physio-Control Inc.), which is widely employed in emergency medicine and ideal in an experimental setting due to its high standardization. Asphyxial cardiac arrest was induced in 10 German hybrid landrace pigs and cardiopulmonary resuscitation was performed according to ERC/AHA 2015 guidelines with mechanical chest compressions. Hemodynamics were measured in the carotid and pulmonary artery. Furthermore, arterial blood gas was drawn to assess oxygenation and tissue perfusion. The custom-designed resuscitation board in combination with the LUCAS® device demonstrated highly sufficient performance regarding hemodynamics during CPR (mean arterial blood pressure, MAP 46 ± 1 mmHg and mean pulmonary artery pressure, mPAP of 36 ± 1 mmHg over the course of CPR). MAP returned to baseline values at 2 h after ROSC (80 ± 4 mmHg), requiring moderate doses of vasopressors. Furthermore, stroke volume and contractility were analyzed using pulse contour analysis (106 ± 3 ml and 1097 ± 22 mmHg/s during CPR). Blood gas analysis revealed CPR-typical changes, normalizing in the due course. Thermodilution parameters did not show persistent intravascular volume shift. Conclusion Standardized cardiopulmonary resuscitation is feasible in a porcine model, achieving adequate hemodynamics and consecutive tissue perfusion of consistent quality.
Published: 2018
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45. Critical care admission following elective surgery was not associated with survival benefit

Author: Kahan, Brennan C., Desponia, Koulenti, Kostoula, Arvaniti, Vanessa, Beavis, Douglas, Campbell, Matthew, Chan, Rui, Moreno, Pearse, Rupert M., Scott, Beattie, Pierre-Alain, Clavien, Nicolas, Demartines, Lee, A Fleisher, Mike, Grocott, James, Haddow, Andreas, Hoeft, Peter, Holt, Naomi, Pritchard, Andrew, Rhodes, Duminda, Wijeysundera, Matt, Wilson, Tahania, Ahmed, Kirsty, Everingham, Russell, Hewson, Marta, Januszewska, Rupert, M Pearse, Mandeep-Kaur, Phull, Richard, Halliwell, Mark, Shulman, Paul, Myles, Werner, Schmid, Michael, Hiesmayr, Patrick, Wouters, Stefan de Hert, Suzana, Lobo, Xiangming, Fang, Lars, Rasmussen, Emmanuel, Futier, Matthieu, Biais, Aurélien, Venara, Karem, Slim, Michael, Sander, Despoina, Koulenti, Mathew, Chan, Atul, Kulkarni, Susilo, Chandra, Aida, Tantri, Emad, Geddoa, Muntadhar, Abbas, Giorgio Della Rocca, Datin, Sivasakthi, Marzida, Mansor, Pastor, Luna, Arthur, Bouwman, Wolfgang, Buhre, Tim, Short, Tunde, Osinaike, Ricardo, Matos, Ioana, Grigoras, Mikhail, Kirov, Denis, Protsenko, Bruce, Biccard, Cesar, Aldecoa, Michelle, Chew, Christoph, Hofer, Martin, Hubner, James, Ditai, Tamas, Szakmany, Lee, Fleisher, Marissa, Ferguson, Michael, Macmahon, Ritchie, Cherian, Helen, Currow, Kathirgamanathan, Kanathiban, David, Gillespie, Edward, Pathmanathan, Katherine, Phillips, Jenifer, Reynolds, Joanne, Rowley, Jeanene, Douglas, Ross, Kerridge, Sameer, Garg, Michael, Bennett, Megha, Jain, David, Alcock, Nico, Terblanche, Rochelle, Cotter, Kate, Leslie, Marcelle, Stewart, Nicolette, Zingerle, Antony, Clyde, Oliver, Hambidge, Adam, Rehak, Sharon, Cotterell, Wilson Binh Quan Huynh, Timothy, Mcculloch, Erez, Ben-Menachem, Thomas, Egan, Jennifer, Cope, Paul, Fellinger, Simone, Haselberger, Caroline, Holaubek, Paul, Lichtenegger, Florian, Scherz, Franz, Hoffer, Veronika, Cakova, Andreas, Eichwalder, Norbert, Fischbach, Reinhold, Klug, Elisabeth, Schneider, Martin, Vesely, Reinhart, Wickenhauser, Karl Gernot Grubmueller, Marion, Leitgeb, Friedrich, Lang, Nancy, Toro, Marlene, Bauer, Friedrich, Laengle, Thomas, Mayrhofer, Christian, Buerkle, Karin, Forstner, Reinhard, Germann, Harald, Rinoesl, Elke, Schindler, Ernst, Trampitsch, Gerhard, Fritsch, Christian, Szabo, Jawad, Bidgoli, Hans, Verdoodt, Patrice, Forget, David, Kahn, Fernande, Lois, Mona, Momeni, Caroline, Prégardien, Audrey, Pospiech, Arnaud, Steyaert, Laurent, Veevaete, Dirk De Kegel, Karen De Jongh, Luc, Foubert, Carine, Smitz, Marcel, Vercauteren, Jan, Poelaert, Veerle Van Mossevelde, Jacques, Abeloos, Stefaan, Bouchez, Marc, Coppens, Luc De Baerdemaeker, Isabel, Deblaere, Ann De Bruyne, Stefan De Hert, Kristine, Fonck, Bjorn, Heyse, Tom, Jacobs, Koen, Lapage, Anneliese, Moerman, Martine, Neckebroek, Aliaksandra, Parashchanka, Nathalie, Roels, Nancy Van Den Eynde, Michael, Vandenheuvel, Jurgen Van Limmen, Ann, Vanluchene, Caroline, Vanpeteghem, Piet, Wyffels, Christel, Huygens, Punitha, Vandenbempt, Marc Van de Velde, Dimitri, Dylst, Bruno, Janssen, Evelien, Schreurs, Fábia Berganton Aleixo, Keulle, Candido, Hugo Dias Batista, Mario, Guimarães, Jaqueline, Guizeline, João, Hoffmann, Suzana, M Lobo, Francisco Ricardo Lobo, Vinícius, Nascimento, Katia, Nishiyama, Lucas, Pazetto, Daniela, Souza, Rodrigo Souza Rodrigues, Ana Maria Vilela Dos Santos, Jaquelline, Jardim, Joao, Silva, Paulo do Nascimento Junior, Thalissa Hermínia Baio, Gabriel Isaac Pereira de Castro, Henri Roger Watanabe Oliveira, Cristina Prata Amendola, Gutemberg, Cardoso, Daniela, Ortega, Ana Flavia Brotto, Mirella Cristine De Oliveira, Álvaro, Réa-Neto, Fernando, Dias, Pedro, Azambuja, Marcos Freitas Knibel, Antonio, Martins, William, Almeida, Calim Neder Neto, Maria Angela Tardelli, Eliana, Caser, Marcio, Machado, Crisitiano, Aguzzoli, Sérgio, Baldisserotto, Fernanda Beck Tabajara, Fernanda, Bettega, La Hore Correa Rodrigues Júnior, Julia de Gasperi, Lais, Faina, Marcos Farias Nolasco, Bruna Ferreira da Costa Fischer, Mariana Fosch de Campos Ferreira, Cristina, Hartmann, Marta, Kliemann, Gustavo Luis Hubert Ribeiro, Julia Merladete Fraga, Thiago Motta Netto, Laura Valduga Pozza, Paulo Rafael Wendling, Caroline, Azevedo, Juliana, Garcia, Marcel, Lopes, Bernardo, Maia, Paula, Maselli, Ralph, Melo, Weslley, Mendes, Matheus, Neves, Jacqueline, Ney, Claudio, Piras, Christopher, Applewhaite, Adrienne, Carr, Lorraine, Chow, Kaylene, Duttchen, Julena, Foglia, Michael, Greene, Ashley, Hinther, Kendra, Houston, Thomas Jared McCormick, Jennifer, Mikhayel, Sam, Montasser, Alex, Ragan, Andrew, Suen, Adrianna, Woolsey, Hai Chuan Yu, Duane, Funk, Stephen, Kowalski, Regina, Legaspi, Heather, Mcdonald, Faisal, Siddiqui, Jeremy, Pridham, Bernadette, Rowe, Sonia, Sampson, Barton, Thiessen, Geoff, Zbitnew, Andre, Bernard, Ronald, George, Philip, Jones, Rita, Moor, Naveed, Siddiqui, Alexandra, Wolfer, Diem, Tran, Denyse, Winch, Gary, Dobson, Thomas, Mccormick, Osama, Montasser, Richard, Hall, Leyla, Baghirzada, Si Yuan Dai, Gregory, Hare, Esther, Lee, Uma, Shastri, Albert, Tsui, Anmol, Yagnik, Danielle, Alvares, Stephen, Choi, Heather, Dwyer, Kathrina, Flores, Colin, Mccartney, Priya, Somascanthan, Carroll, Jo, Janneth, Pazmino-Canizares, Noam, Ami, Vincent, Chan, Anahi, Perlas, Ruth, Argue, Katie, Lavis, Kelly, Mayson, Ying, Cao, Hong, Gao, Tingju, Hu, Jie, Lv, Jian, Yang, Yang, Yang, Zhong, Yi, Jing, Zhou, Xiaohua, Zou, Miao, He, Xiaoying, Li, Dihuan, Luo, Haiying, Wang, Tian, Yu, Liyong, Chen, Lijun, Wang, Yunfei, Cai, Zhongming, Cao, Yanling, Li, Jiaxin, Lian, Haiyun, Sun, Sheng, Wang, Zhipeng, Wang, Kenru, Wang, Zhu, Yi, Xindan, Du, Hao, Fan, Yunbin, Fu, Lixia, Huang, Yanming, Huang, Haifang, Hwan, Hong, Luo, Pi-Sheng, Qu, Fan, Tao, Zhen, Wang, Guoxiang, Wang, Shun, Wang, Yan, Zhang, Xiaolin, Zhang, Chao, Chen, Weixing, Wang, Zhengyuan, Liu, Lihua, Fan, Jing, Tang, Yijun, Chen, Yongjie, Chen, Yangyang, Han, Changshun, Huang, Guojin, Liang, Jing, Shen, Jun, Wang, Qiuhong, Yang, Jungang, Zhen, Haidong, Zhou, Junping, Chen, Zhang, Chen, Xiaoyu, Li, Meng, Bo, Haiwang, Ye, Xiaoyan, Zhang, Yanbing, Bi, Jianqiao, Cao, Fengying, Guo, Hong, Lin, Yang, Liu, Meng, Lv, Pengcai, Shi, Xiumei, Song, Chuanyu, Sun, Yongtao, Sun, Yuelan, Wang, Shenhui, Wang, Min, Zhang, Rong, Chen, Jiabao, Hou, Yan, Leng, Qing-Tao, Meng, Qian, Li, Zi-Ying, Shen, Zhong-Yuan, Xia, Rui, Xue, Yuan, Zhang, Zhao, Bo, Xian-Jin, Zhou, Qiang, Chen, Huinan, Guo, Yongqing, Guo, Yuehong, Qi, Zhi, Wang, Jianfeng, Wei, Weiwei, Zhang, Lina, Zheng, Bao, Qi, Yaqiu, Chen, Yijiao, Chen, Yue, Fei, Nianqiang, Hu, Xuming, Hu, Min, Lei, Xiaoqin, Li, Xiaocui, Lv, Fangfang, Miao, Lingling, Ouyang, Qian, Lu, Conyu, Shen, Sun, Yu, Yuting, Wang, Dong, Wang, Chao, Wu, Liyuan, Xu, Jiaqi, Yuan, Lina, Zhang, Huan, Zhang, Yapping, Zhang, Jinning, Zhao, Chong, Zhao, Lei, Zhao, Tianzhao, Zheng, Dachun, Zhou, Haiyan, Zhou, Zhou, Ce, Kaizhi, Lu, Ting, Zhao, Changlin, He, Hong, Chen, Shasha, Chen, Baoli, Cheng, Jie, He, Lin, Jin, Caixia, Li, Hui, Li, Yuanming, Pan, Yugang, Shi, Xiao Hong Wen, Shuijing, Wu, Guohao, Xie, Kai, Zhang, Bing, Zhao, Xianfu, Lu, Feifei, Chen, Qisheng, Liang, Xuewu, Lin, Yunzhi, Ling, Gang, Liu, Jing, Tao, Yang, Lu, Jialong, Zhou, Fumei, Chen, Yunlin, Feng, Benchao, Hou, Jiamei, Lin, Mei, Liu, Foquan, Luo, Xiaoyun, Shi, Yingfen, Xiong, Lin, Xu, Shuangjia, Yang, Qin, Zhang, Huaigen, Zhang, Weihong, Zhao, Weilu, Zhao, Yun, Bai, Linbi, Chen, Sijia, Chen, Qinxue, Dai, Wujun, Geng, Kunyuan, Han, Xin, He, Luping, Huang, Binbin, Ji, Danyun, Jia, Shenhui, Jin, Qianjun, Li, Dongdong, Liang, Shan, Luo, Lulu, Lwang, Yunchang, Mo, Yuanyuan, Pan, Xinyu, Qi, Meizi, Qian, Jinling, Qin, Yelong, Ren, Yiyi, Shi, Junlu, Wang, Junkai, Wang, Leilei, Wang, Junjie, Xie, Yixiu, Yan, Yurui, Yao, Mingxiao, Zhang, Jiashi, Zhao, Xiuxiu, Zhuang, Yanqiu, Ai, Fang, Du, Long, He, Ledan, Huang, Zhisong, Li, Huijuan, Li, Yetong, Li, Liwei, Li, Meng, Su, Yazhuo, Yuan, Enman, Zhang, Jie, Zhang, Shuna, Zhao, Zhenrong, Ji, Ling, Pei, Wang, Li, Chen, Chen, Beibei, Dong, Jing, Li, 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Strydom, Edwin, Wilberforce-Turton, Rubendraj, R Chetty, Subash, Chirkut, Larissa, Cronje, Kim de Vasconcellos, Nokukhanya, Z Dube, N Sibusiso Gama, Garyth, M Green, Randolph, Green-Thompson, Suman Mewa Kinoo, Prenolin, Kistnasami, Kapil, Maharaj, Manogaran, S Moodley, Sibongile, J Mothae, Ruvashni, Naidoo, Aslam, M, Noorbhai, F, Vivesh, Rughubar, Jenendhiran, Reddy, Avesh, Singh, David, L Skinner, Murray, J Smith, Bhagwan, Singh, Ravi, Misra, Maheshwar, Naidoo, Pireshin, Ramdharee, Yvonne, Selibea, Selina, Sewpersad, Shailendra, Sham, Joseph, D Wessels, Cucu, Africander, Tarek, Bejia, Stephen, P Blakemore, Marisa, Botes, Bimalshakth, Bunwarie, Carlos, B Hernandez, Mohammud, A Jeeraz, Dagmara, A Legutko, Acela, G Lopez, Jenine, N De Meyer, Tanaka, Muzenda, Noel, Naidoo, Maryam, Patel, Rao, Pentela, Marina, Junge, Naj, Mansoor, Lana, Rademan, Pawel, Scislowski, Ismail, Seedat, Bianca van den Berg, Doreen van der Merwe, Steyn van Wyk, Komalan, Govender, Darshan, Naicker, Rajesh, Ramjee, 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Friedrich, Mayrhofer, Thoma, Buerkle, Christian, Forstner, Karin, Germann, Reinhard, Rinoesl, Harald, Schindler, Elke, Trampitsch, Ernst, Fritsch, Gerhard, Szabo, Christian, Bidgoli, Jawad, Verdoodt, Han, Forget, Patrice, Kahn, David, Lois, Fernande, Momeni, Mona, Prégardien, Caroline, Pospiech, Audrey, Steyaert, Arnaud, Veevaete, Laurent, De Kegel, Dirk, De Jongh, Karen, Foubert, Luc, Smitz, Carine, Vercauteren, Marcel, Poelaert, Jan, Van Mossevelde, Veerle, Abeloos, Jacque, Bouchez, Stefaan, Coppens, Marc, De Baerdemaeker, Luc, Deblaere, Isabel, De Bruyne, Ann, De Hert, Stefan, Fonck, Kristine, Heyse, Bjorn, Jacobs, Tom, Lapage, Koen, Moerman, Anneliese, Neckebroek, Martine, Parashchanka, Aliaksandra, Roels, Nathalie, Van Den Eynde, Nancy, Vandenheuvel, Michael, Van Limmen, Jurgen, Vanluchene, Ann, Vanpeteghem, Caroline, Wyffels, Piet, Huygens, Christel, Vandenbempt, Punitha, Van de Velde, Marc, Dylst, Dimitri, Janssen, Bruno, Schreurs, Evelien, Aleixo, Fábia Berganton, Candido, Keulle, Dias Batista, Hugo, Guimarães, Mario, Guizeline, Jaqueline, Hoffmann, João, Lobo, Suzana M., Lobo, Francisco Ricardo, Nascimento, Viníciu, Nishiyama, Katia, Pazetto, Luca, Souza, Daniela, Souza Rodrigues, Rodrigo, Vilela dos Santos, Ana Maria, Jardim, Jaquelline, Silva, Joao, do Nascimento Junior, Paulo, Baio, Thalissa Hermínia, Pereira de Castro, Gabriel Isaac, Watanabe Oliveira, Henri Roger, Amendola, Cristina Prata, Cardoso, Gutemberg, Ortega, Daniela, Brotto, Ana Flavia, De Oliveira, Mirella Cristine, Réa-Neto, Álvaro, Dias, Fernando, Azambuja, Pedro, Knibel, Marcos Freita, Martins, Antonio, Almeida, William, Neto, Calim Neder, Tardelli, Maria Angela, Caser, Eliana, Machado, Marcio, Aguzzoli, Crisitiano, Baldisserotto, Sérgio, Beck Tabajara, Fernanda, Bettega, Fernanda, Rodrigues Júnior, La Hore Correa, de Gasperi, Julia, Faina, Lai, Nolasco, Marcos Faria, da Costa Fischer, Bruna Ferreira, de Campos Ferreira, Mariana Fosch, Hartmann, Cristina, Kliemann, Marta, Ribeiro, Gustavo Luis Hubert, Fraga, Julia Merladete, Netto, Thiago Motta, Pozza, Laura Valduga, Wendling, Paulo Rafael, Azevedo, Caroline, Garcia, Juliana, Lopes, Marcel, Maia, Bernardo, Maselli, Paula, Melo, Ralph, Mendes, Weslley, Neves, Matheu, Ney, Jacqueline, Piras, Claudio, Applewhaite, Christopher, Carr, Adrienne, Chow, Lorraine, Duttchen, Kaylene, Foglia, Julena, Greene, Michael, Hinther, Ashley, Houston, Kendra, McCormick, Thomas Jared, Mikhayel, Jennifer, Montasser, Sam, Ragan, Alex, Suen, Andrew, Woolsey, Adrianna, Yu, Hai Chuan, Funk, Duane, Kowalski, Stephen, Legaspi, Regina, McDonald, Heather, Siddiqui, Faisal, Pridham, Jeremy, Rowe, Bernadette, Sampson, Sonia, Thiessen, Barton, Zbitnew, Geoff, Bernard, Andre, George, Ronald, Jones, Philip, Moor, Rita, Siddiqui, Naveed, Wolfer, Alexandra, Tran, Diem, Winch, Denyse, Dobson, Gary, McCormick, Thoma, Montasser, Osama, Hall, Richard, Baghirzada, Leyla, Dai, Si Yuan, Hare, Gregory, Lee, Esther, Shastri, Uma, Tsui, Albert, Yagnik, Anmol, Alvares, Danielle, Choi, Stephen, Dwyer, Heather, Flores, Kathrina, McCartney, Colin, Somascanthan, Priya, Carroll, Jo, Pazmino-Canizares, Janneth, Ami, Noam, Chan, Vincent, Perlas, Anahi, Argue, Ruth, Lavis, Katie, Mayson, Kelly, Cao, Ying, Gao, Hong, Hu, Tingju, Lv, Jie, Yang, Jian, Yang, Yang, Zhong, Yi, Zhou, Jing, Zou, Xiaohua, He, Miao, Li, Xiaoying, Luo, Dihuan, Wang, Haiying, Yu, Tian, Chen, Liyong, Wang, Lijun, Cai, Yunfei, Cao, Zhongming, Li, Yanling, Lian, Jiaxin, Sun, Haiyun, Wang, Sheng, Wang, Zhipeng, Wang, Kenru, Zhu, Yi, Du, Xindan, Fan, Hao, Fu, Yunbin, Huang, Lixia, Huang, Yanming, Hwan, Haifang, Luo, Hong, Qu, Pi-Sheng, Tao, Fan, Wang, Zhen, Wang, Guoxiang, Wang, Shun, Zhang, Yan, Zhang, Xiaolin, Chen, Chao, Wang, Weixing, Liu, Zhengyuan, Fan, Lihua, Tang, Jing, Chen, Yijun, Chen, Yongjie, Han, Yangyang, Huang, Changshun, Liang, Guojin, Shen, Jing, Wang, Jun, Yang, Qiuhong, Zhen, Jungang, Zhou, Haidong, Chen, Junping, Chen, Zhang, Li, Xiaoyu, Meng, Bo, Ye, 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Guohao, Zhang, Kai, Zhao, Bing, Lu, Xianfu, Chen, Feifei, Liang, Qisheng, Lin, Xuewu, Ling, Yunzhi, Liu, Gang, Tao, Jing, Yang, Lu, Zhou, Jialong, Chen, Fumei, Feng, Yunlin, Hou, Benchao, Lin, Jiamei, Liu, Mei, Luo, Foquan, Shi, Xiaoyun, Xiong, Yingfen, Xu, Lin, Yang, Shuangjia, Zhang, Qin, Zhang, Huaigen, Zhao, Weihong, Zhao, Weilu, Bai, Yun, Chen, Linbi, Chen, Sijia, Dai, Qinxue, Geng, Wujun, Han, Kunyuan, He, Xin, Huang, Luping, Ji, Binbin, Jia, Danyun, Jin, Shenhui, Li, Qianjun, Liang, Dongdong, Luo, Shan, Lwang, Lulu, Mo, Yunchang, Pan, Yuanyuan, Qi, Xinyu, Qian, Meizi, Qin, Jinling, Ren, Yelong, Shi, Yiyi, Wang, Junlu, Wang, Junkai, Wang, Leilei, Xie, Junjie, Yan, Yixiu, Yao, Yurui, Zhang, Mingxiao, Zhao, Jiashi, Zhuang, Xiuxiu, Ai, Yanqiu, Du, Fang, He, Long, Huang, Ledan, Li, Zhisong, Li, Huijuan, Li, Yetong, Li, Liwei, Meng, Su, Yuan, Yazhuo, Zhang, Enman, Zhang, Jie, Zhao, Shuna, Ji, Zhenrong, Pei, Ling, Wang, Li, Chen, Chen, Dong, Beibei, Li, Jing, Miao, Ziqiang, Mu, 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Ganter, Donna Louise, McCann, Lloyd, Foley, Julia, Gilmour, Fiona, Lumsden, Rachelle, Moores, Mark, Olliff, Sue, Sardareva, Elitza, Tai, Joyce, Wikner, Matthew, Wong, Christopher, Chaddock, Mark, Czepanski, Carolyn, McKendry, Patrick, Polakovic, Daniel, Polakovich, Daniel, Robert, Axe, Tormo Belda, Margarita, Norton, Tracy, Alherz, Fadhel, Barneto, Lisa, Ramirez, Alberto, Sayeed, Ahmed, Smith, Nicola, Bennett, Cambell, McQuoid, Shane, Jansen, Tracy-Lee, Nico, Zin, Scott, John, Freschini, David, Freschini, Angela, Hopkins, Brian, Manson, Lara, Stoltz, Deon, Bates, Alexander, Davis, Simon, Freeman, Victoria, McGaughran, Lynette, Baskar Sharma, Swarna, Burrows, Tom, Byrne, Kelly, English, Duane, Johnson, Robert, Chai Law, Kiew, Manikkam, Brendon, Naidoo, Shaun, Rumball, Margot, Whittle, Nicola, Franks, Romilla, Gibson-Lapsley, Hannah, Salter, Ryan, Walsh, Dean, Cooper, Richard, Perry, Katherine, Obobolo, Amo, Sule, Umar Musa, Ahmad, Abdurrahman, Atiku, Mamuda, Mohammed, Alhassan Datti, Sarki, Adamu Muhammad, Adekola, Oyebola, Akanmu, Olanrewaju, Durodola, Akanmu, Olukoju, Olusegun, Raji, Victor, Olajumoke, Tokunbo, Oyebamiji, Emmanuel, Adenekan, Anthony, Adetoye, Adenekan, Faponle, Folayemi, Olateju, Simeon, Owojuyigbe, Afolabi, Talabi, Ademola, Adenike, Odewabi, Adewale, Badru, Collins, Nwokoro, Ezekiel, Emmanuel, Fatungase, Oluwabunmi Motunrayo, Grace, Anuforo, Sola, Sotannde, Stella, Ogunmuyiwa, Ademola, Adeyinka, Adeolu, Augustine A., Adigun, Tinuolac, Akinwale, Mukaila, Fasina, Oluyemi, Gbolahan, Olalere, Idowu, Olusola, Olonisakin, Rotimi Peter, Osinaike, Babatunde Babasola, Asudo, Felicia, Mshelia, Danladi, Abdur-Rahman, Lukman, Agodirin, Olayide, Bello, Jibril, Bolaji, Benjamin, Oyedepo, Olanrewaju Olubukola, Ezike, Humphrey, Iloabachie, Ikechukwu, Okonkwo, Ikemefuna, Onuora, Elia, Onyeka, Tonia, Ugwu, Innocent, Umeh, Friday, Alagbe-Briggs, Olubusola, Dodiyi-Manuel, Amabra, Echem, Richard, Obasuyi, Bright, Onajin-Obembe, Bisola, Bandeira, Maria Expedito, Martins, Alda, Tomé, Miguel, Martins Costa, Ana Cristina Miranda, Krystopchuk, Andriy, Branco, Teresa, Esteves, Simao, Melo, Marco António, Monte, Júlia, Rua, Fernando, Martins, Isabel, Pinho-Oliveira, Vítor Miguel, Rodrigues, Carla Maria, Cabral, Raquel, Marques, Sofia, Rêgo, Sara, Teixeira Jesus, Joana Sofia, Conceição Marques, Maria, Romao, Cristina, Dias, Sandra, Santos, Ana Margarida, Alves, Maria Joao, Salta, Cristina, Cruz, Salome, Duarte, Célia, Furtado Paiva, António Armando, do Nascimento Cabral, Tiago, Fariae Maia, Dionisio, Correia da Silva, Rui Freitas Mendonça, Langner, Anuschka, Oliveira Resendes, Hernâni, da Conceição Soares, Maria, Abrunhosa, Alexandra, Faria, Filomena, Miranda, Lina, Pereira, Helena, Serra, Sofia, Ionescu, Daniela, Margarit, Simona, Mitre, Calin, Vasian, Horatiu, Manga, Gratiela, Stefan, Andreea, Tomescu, Dana, Filipescu, Daniela, Paunescu, Marilena-Alina, Stefan, Mihai, Stoica, Radu, Gavril, Laura, Pătrăşcanu, Emilia, Ristescu, Irina, Rusu, Daniel, Diaconescu, Ciresica, Iosep, Gabriel Florin, Pulbere, Dorin, Ursu, Irina, Balanescu, Andreea, Grintescu, Ioana, Mirea, Liliana, Rentea, Irina, Vartic, Mihaela, Lupu, Mary-Nicoleta, Stanescu, Dorin, Streanga, Lavinea, Antal, Oana, Hagau, Natalia, Patras, Dumitru, Petrisor, Cristina, Tosa, Flaviu, Tranca, Sebastian, Copotoiu, Sanda Maria, Ungureanu, Liviu Lucian, Harsan, Cristian Remu, Papurica, Mariu, Cernea, Daniela Denisa, Dragoescu, Nicoleta Alice, Aflori, Laura, Vaida, Carmen, Ciobotaru, Oana Roxana, Aignatoaie, Mariana, Carp, Cristina Paula, Cobzaru, Isabelle, Mardare, Oana, Purcarin, Bianca, Tutunaru, Valentin, Ionita, Victor, Arustei, Mirela, Codita, Anisoara, Busuioc, Mihai, Chilinciuc, Ion, Ciobanu, Cristina, Belciu, Ioana, Tincu, Eugen, Blaj, Mihaela, Grosu, Ramona-Mihaela, Sandu, Gigel, Bruma, Dana, Corneci, Dan, Dutu, Madalina, Krepil, Adriana, Copaciu, Elena, Dumitrascu, Clementina Oana, Jemna, Ramona, Mihaescu, Florentina, Petre, Raluca, Tudor, Cristina, Ursache, Elena, Kulikov, Alexander, Lubnin, Andrey, Grigoryev, Evgeny, Pugachev, Stanislav, Tolmasov, Alexander, Hussain, Ayyaz, Ilyina, Yana, Roshchina, Anna, Iurin, Aleksandr, Chazova, Elena, Dunay, Artem, Karelov, Alexey, Khvedelidze, Irina, Voldaeva, Olga, Belskiy, Vladislav, Dzhamullaev, Parvin, Grishkowez, Elena, Kretov, Vladimir, Levin, Valeriy, Molkov, Aleksandr, Puzanov, Sergey, Samoilenko, Aleksandr, Tchekulaev, Aleksandr, Tulupova, Valentina, Utkin, Ivan, Allorto, Nikki Leigh, Bishop, David Gray, Builu, Pierre Monji, Cairns, Carel, Dasrath, Ashish, de Wet, Jacque, den Hoedt, Marielle, Grey, Ben, Hayes, Morgan Philip, Küsel, Belinda Senta, Shangase, Nomcebo, Wise, Robert, Cacala, Sharon, Farina, Zane, Govindasamy, Vishendran, Kruse, Carl-Heinz, Lee, Carolyn, Marais, Leonard, Naidoo, Thinagrin Dhasarthun, Rajah, Chantal, Rodseth, Reitze Nil, Ryan, Lisa, von Rhaden, Richard, Adam, Suwayba, Alphonsus, Christella, Ameer, Yusuf, Anderson, Frank, Basanth, Sujith, Bechan, Sudha, Bhula, Chettan, Biccard, Bruce M., Biyase, Thuli, Buccimazza, Ine, Cardosa, Jorge, Chen, Jame, Daya, Bhavika, Drummond, Leanne, Elabib, Ali, Goad, Ehab Helmy Abdel, Goga, Ismail E., Goga, Riaz, Harrichandparsad, R., Hodgson, Richard E., Jordaan, J., Kalafatis, Nicky, Kampik, Christian, Landers, At, Loots, Emil, Madansein, Rajhmum, Madaree, Anil, Madiba, Thandinkosi E., Manzini, Vukani T., Mbuyisa, Mbali, Moodley, Rajan, Msomi, Mduduzi, Mukama, Innocent, Naidoo, Desigan, Naidoo, Rubeshan, Naidu, Tesuven K., Ntloko, Sindiswa, Padayachee, Eneshia, Padayachee, Lucelle, Phaff, Martijn, Pillay, Bala, Pillay, Desigan, Pillay, Lutchmee, Ramnarain, Anupa, Ramphal, Suren R., Ryan, Paul, Saloojee, Ahmed, Sebitloane, Motshedisi, Sigcu, Noluyolo, Taylor, Jenna L., Torborg, Alexandra, Visser, Linda, Anderson, Philip, Conradie, Alae, de Swardt, Mathew, de Villiers, Martin, Eikman, Johan, Liebenberg, Riaan, Mouton, Johan, Paton, Abbey, van der Merwe, Louwrence, Wilscott-Davids, Candice, Barrett, Wendy Joan, Bester, Marlet, de Beer, Johan, Geldenhuys, Jacque, Gouws, Hanni, Potgieter, Jan-Hendrik, Strydom, Magdel, Wilberforce-Turton, Edwin, Chetty, Rubendraj R., Chirkut, Subash, Cronje, Larissa, de Vasconcellos, Kim, Dube, Nokukhanya Z., Sibusiso Gama, N., Green, Garyth M., Green-Thompson, Randolph, Kinoo, Suman Mewa, Kistnasami, Prenolin, Maharaj, Kapil, Moodley, Manogaran S., Mothae, Sibongile J., Naidoo, Ruvashni, Aslam, M., Noorbhai, F., Rughubar, Vivesh, Reddy, Jenendhiran, Singh, Avesh, Skinner, David L., Smith, Murray J., Singh, Bhagwan, Misra, Ravi, Naidoo, Maheshwar, Ramdharee, Pireshin, Selibea, Yvonne, Sewpersad, Selina, Sham, Shailendra, Wessels, Joseph D., Africander, Cucu, Bejia, Tarek, Blakemore, Stephen P., Botes, Marisa, Bunwarie, Bimalshakth, Hernandez, Carlos B., Jeeraz, Mohammud A., Legutko, Dagmara A., Lopez, Acela G., De Meyer, Jenine N., Muzenda, Tanaka, Naidoo, Noel, Patel, Maryam, Pentela, Rao, Junge, Marina, Mansoor, Naj, Rademan, Lana, Scislowski, Pawel, Seedat, Ismail, 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Delgado García, David R., Zamudio, Diana, Garcia Del Valle, Santiago, Luz Serrano, M., Alonso, Eduardo, Anillo, Victor, Maseda, Emilio, Salgado, Patricia, Suarez, Lui, Suarez-de-la-Rica, Alejandro, Villagrán, María José, Alonso, José Ignacio, Cabezuelo, Estefania, Garcia-Saiz, Irene, Lopez del Moral, Olga, Martín, Silvia, Perez Gonzalez, Alba, Tovar Doncel, Sherezade, Vera, Martin Agüero, Ávila Sánchez, Francisco José, Castaño, Beatriz, Castaño Moreira, Beatriz, Flores Risco, Sahely, Paz Martín, Daniel, Pérez Martín, Fernando, Poza, Paloma, Ruiz, Adela, Serna Martínez, Wilson Fabio, Vicente, Bárbara Vázquez, Dominguez, Saul Velaz, Fernández, Salvador, Munoz-López, Alfonso, Bernat, Maria Jose, Mas, Arantxa, Planas, Kenneth, Jawad, Monir, Saeed, Yousif, Hedin, Annika, Levander, Helena, Holmström, Sandra, Lönn, David, Zoerner, Frank, Åkring, Irene, Widmark, Carl, Zettergren, Jan, Liljequist, Victor Aspelund, Nystrom, Lena, Odeberg-Wernerman, Suzanne, Oldner, Ander, Reje, Patrik, Lyckner, 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Dempsey, Ged, Seasman, Colette, Basit Nawaz Khan, Raja, Kurasz, Claire, Macgregor, Mark, Shawki, Burhan, Hariharan, Vimal, Chau, Simon, Ellis, Kate, Butt, Georgina, Chicken, Dennis-Wayne, Christmas, Natasha, Allen, Samantha, Daniel, Gayatri Daniel, Dempster, Angie, Kemp, Juliette, Matthews, Lewi, Mcglone, Philip, Tambellini, Joanne, Trodd, Dawn, Freitas, Katie, Garg, Atul, Karpate, Shilpaja, Kulkarni, Aditi, O’Hara, Chloe, Troko, Jtroko, Angus, Kirsty, Bradley, Jacqueline, Brennan, Emma, Brooks, Carolyn, Brown, Janette, Brown, Gemma, Finch, Amanda, Gratrix, Karen, Hesketh, Sue, Hill, Gillian, Jeffs, Carol, Morgan, Maureen, Pemberton, Chri, Slawson, Nicola, Spickett, Helen, Swarbrick, Gemma, Thomas, Megan, Van Duyvenvoorde, Greta, Brennan, Andrew, Briscoe, Richard, Cooper, Sarah, Lawton, Tom, Northey, Martin, Senaratne, Rashmi, Stanworth, Helen, Burrows, Lorna, Cain, Helen, Craven, Rachael, Davies, Keith, Jonas, Attila, Pachucki, Marcin, Walkden, Graham, Davies, Helen, Gudaca, 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Amir, Shekar, Priya, Harden, Catherine, Hollands, Heidi, King, Angela, March, Linda, Minto, Gary, Patrick, Abigail, Waugh, Darren, Kumara, Paramesh, Simeson, Karen, Yarwood, Jamie, Browning, Julie, Hatton, Jonathan, Julian, Howe, Mitra, Atideb, Newton, Maria, Pernu, Pawan, Wilson, Alison, Commey, Thelma, Foot, Helen, Glover, Lyn, Gupta, Ajay, Lancaster, Nicola, Levin, Jill, Mackenzie, Felicity, Mestanza, Claire, Nofal, Emma, Pout, Lauren, Varden, Rosanna, Wild, Jonathan, Jones, Stephanie, Moreton, Sarah, Pulletz, Mark, Davies, Charlotte, Martin, Matthew, Thomas, Sian, Burns, Karen, McArthur, Carol, Patel, Panna, Lau, Gary, Rich, Natalie, Davis, Fiona, Lyons, Rachel, Port, Beth, Prout, Rachel, Smith, Christopher, Adelaja, Yemi, Bennett, Victoria, Bidd, Heena, Dumitrescu, Alexandra, Murphy, Jacqui Fox, Keen, Abigail, Mguni, Nhlanhla, Ong, Cheng, Adams, George, Boshier, Pier, Brown, Richard, Butryn, Izabella, Chatterjee, Jayanta, Freethy, Alexander, Lockwood, Geoffrey, Tsakok, Maria, Tsiligiannis, Sophia, Peat, William, Stephenson, Lorraine, Bradburn, Mike, Pick, Sara, Cunha, Pedro, Olagbaiye, Olufemi, Tayeh, Salim, Abernethy, Caroline, Balasubramaniam, Madhu, Bennett, Rachael, Bolton, David, Martinson, Victoria, Naylor, Charde, Bell, Stephanie, Heather, Blaylock, Kushakovsky, Vlad, Alcock, Liam, Alexander, Hazel, Anderson, Colette, Baker, Paul, Brookes, Morag, Cawthorn, Louise, Cirstea, Emanuel, Colling, Kerry, Coulter, Ian, Das, Suparna, Haigh, Kathryn, Hamdan, Alhafidz, Hugill, Keith, Kottam, Lucksy, Lisseter, Emily, Mawdsley, Matthew, McGivern, Julie, Padala, Krishnaveni, Phelps, Victoria, kumar, Vineshykaa Ramesh, Stewart, Kirsten, Towse, Kayley, Tregonning, Julie, Vahedi, Ali, Walker, Alycon, Baines, Duncan, Bilolikar, Anjali, Chande, Shiv, Copley, Edward, Dunk, Nigel, Kulkarni, Raghavendra, Kumar, Pawan, Metodiev, Yavor, Ncomanzi, Dumisani, Raithatha, Bhavesh, Raymode, Parizade, Szafranski, Jan, Twohey, Linda, Watt, Philip, Weatherall, Lucie, Weatherill, J., Whitman, Zoe, Wighton, Elinor, Abayasinghe, Chamika, Chan, Alexander, Darwish, Sharif, Gill, Jame, Glasgow, Emma, Hadfield, Daniel, Harris, Clair, Kochhar, Arun, Mellis, Clare, Pool, Andrew, Riozzi, Paul, Selman, Andrew, Smith, Emma-Jane, Vele, Liana, Gercek, Yuksel, Guy, Kramer, Holden, Dougla, Watson, Nichola, Whysall, Karen, Andreou, Prematie, Hales, Dawn, Thompson, Jonathan, Bowrey, Sarah, McDonald, Shara, Gilmore, Jemma, Hills, Vicky, Kelly, Chan, Kelly, Sinead, Lloyd, Geraint, Abbott, Tom, Gall, Lewi, Torrance, Hew, Vivian, Mark, Berntsen, Emer, Nolan, Tracey, Turner, Angu, Vohra, Akbar, Brown, Andrew, Clark, Richard, Coughlan, Elaine, Daniel, Conway, Patvardhan, Chinmay, Pearson, Rachel, Predeep, Sheba, Saad, Hesham, Shanmugam, Mohanakrishnan, Varley, Simon, Wylie, Katharine, Cooper, Lucy, Makowski, Arystarch, Misztal, Beata, Moldovan, Eliza, Pegg, Claire, Donovan, Andrew, Foot, Jayne, Large, Simon, Claxton, Andrew, Netke, Bhagyashree, Armstrong, Richard, Calderwood, Claire, Kwok, Andy, Mohr, Otto, Oyeniyi, Peter, Patnaik, Lisa, Post, Benjamin, Ali, Sarah, Arshad, Homa, Baker, Gerard, Brenner, Laura, Brincat, Maximilian, Brunswicker, Annemarie, Cox, Hannah, Cozar, Octavian Ionut, Durst, Alexander, Fengas, Lior, Flatt, Jim, Glister, Georgina, Narwani, Vishal, Photi, Evangelo, Rankin, Adeline, Rosbergen, Melissa, Tan, Mark, Beaton, Ceri, Horn, Rachel, Hunt, Jane, Rousseau, Guy, Stancombe, Lucia, Absar, Mohammed, Allsop, Joanne, Drinkwater, Zoe, Hodgkiss, Tracey, Smith, Kirsty, Brown, Jamie, Alexander-Sefre, Farhad, Campey, Lorraine, Dudgeon, Lucy, Hall, Kathryn, Hitchcock, Rachael, James, Lynne, Smith, Kate, Winstone, Ulrika, Ahmad, Norfaizan, Bauchmuller, Kri, Harrison, Jonathan, Jeffery, Holly, Miller, Duncan, Pinder, Angela, Pothuneedi, Sailaja, Rosser, Jonathan, Sanghera, Sumayer, Swift, Diane, Walker, Rachel, Bester, Delia, Cavanagh, Sarah, Cripps, Heather, Daniel, Harvey, Lynch, Julie, Paton, Alison, Pyke, Shirley, Scholefield, John, Whitworth, Helen, Bottrill, Fiona, Ramalingam, Ganesh, Webb, Stephen, Akerman, Nik, Antill, Philip, Bourner, Lynsey, Buckley, Sarah, Castle, Gail, Charles, Rob, Eggleston, Christopher, Foster, Rebecca, Gill, Satwant, Lindley, Kate, Lklouk, Mohamed, Lowery, Tracey, Martin, Oliver, Milne, David, O’Connor, Patrick, Ratcliffe, Andrew, Rose, Alastair, Smith, Annie, Varma, Sandeep, Ward, Jackie, Barcraft-Barnes, Helena, Camsooksai, Julie, Colvin, Carolyn, Reschreiter, Henrik, Tbaily, Lee, Venner, Nicola, Hamilton, Caroline, Kelly, Lewi, Toth-Tarsoly, Piroska, Dodsworth, Kerry, Foord, Denise, Gordon, Paul, Hawes, Elizabeth, Lamb, Nikki, Mouland, Johanna, Nightingale, Jeremy, Rose, Steve, Schrieber, Joe, Al ‘Amri, Khalid, Aladin, Hafiz, Arshad, Mohammed Asif, Barraclough, Jame, Bentley, Conor, Bergin, Colin, Carrera, Ronald, Clarkson, Aisling, Collins, Michelle, Cooper, Lauren, Denham, Samuel, Griffiths, Ewen, Ip, Peter, Jeyanthan, Somasundaram, Joory, Kavita, Kaur, Satwant, Marriott, Paul, Mitchell, Natalie, 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Graham, Datson, Amanda, Fouracres, Anna, Graterol, Juan, Graves, Lynne, Hong, Bosun, Ishimaru, Alexander, Karthikeyan, Arvind, King, Helen, Lawson, Tom, Lee, Gregory, Lyons, Saoirse, Macalister Hall, Andrew, Mathoulin, Sophie, Mcintyre, Eilidh, Mclaughlin, Danny, Mulcahy, Kathleen, Ratcliffe, Anna, Robbins, Jame, Sung, Weilin, Tayo, Adeoluwa, Trembath, Lisa, Venugopal, Suneetha, Walker, Robert, Wigmore, Geoffrey, Boereboom, Catherine, Downes, Charlotte, Humphries, Ryan, Melbourne, Susan, Smith, Coral, Tou, Samson, Ullah, Shafa, Batchelor, Nick, Boxall, Leigh, Broomby, Rupert, Deen, Tariq, Hellewell, Alistair, Helliwell, Laurence, Hutchings, Melanie, Hutchins, David, Keenan, Samantha, Mackie, Donna, Donna, Alison, Smith, France, Stone, Lucy, Thorpe, Kevin, Wassall, Richard, Woodgate, Andrew, Baillie, Shelley, Campbell, Tara, James, Sarah, King, Chri, Marques de Araujo, Daniela, Martin, Daniel, Morkane, Clare, Neely, Julia, Rajendram, Rajkumar, Burton, Megan, James, Kathryn, Keevil, Edward, Minik, Orsolya, Morgan, Jenna, Musgrave, Anna, Rajanna, Harish, Roberts, Tracey, Adamson, Michael, Jumbe, Sandra, Kendall, Jennie, Muthuswamy, Mohan Babu, Anderson, Charlotte, Cruikshanks, Andrew, Wrench, Ian, Zeidan, Lisa, Ardern, Diane, Harris, Benjamin, Hellstrom, Johanna, Martin, Jane, Thomas, Richard, Varsani, Nimu, Wrey Brown, Caroline, Docherty, Philip, Gillies, Michael, McGregor, Euan, Usher, Helen, Craig, Jayne, Smith, Andrew, Ahmad, Tahania, Bodger, Phoebe, Creary, Thai, Fowler, Alexander, Hewson, Ru, Ijuo, Eke, Jones, Timothy, Kantsedikas, Ilya, Lahiri, Sumitra, McLean, Aaron Lawson, Niebrzegowska, Edyta, Phull, Mandeep, Wang, Difei, Wickboldt, Nadine, Baldwin, Jacqueline, Doyle, Donna, Mcmullan, Sean, Oladapo, Michelle, Owen, Thoma, Williams, Alexandra, Daniel, Hull, Gregory, Peter, Husain, Tauqeer, Kirk-Bayley, Justin, Mathers, Edward, Montague, Laura, White, Stuart, Avis, Joanne, Cook, Tim, Dali-Kemmery, Lola, Kerslake, Ian, Lambourne, Victoria, Pearson, Annabel, Boyd, Christine, Callaghan, Mark, Lawson, Cathy, McCrossan, Roopa, Nesbitt, Vanessa, O’connor, Laura, Scott, Julia, Sinclair, Rhona, Farid, Nahla, Morgese, Ciro, Bhatia, Kailash, Karmarkar, Swati, Ahmed, Jamil, Branagan, Graham, Hutton, Monica, Swain, Andrew, Brookes, Jamie, Cornell, Jonathan, Dolan, Rachael, Hulme, Jonathan, Jansen van Vuuren, Amanda, Jowitt, Tom, Kalashetty, Gunasheela, Lloyd, Fran, Patel, Kiran, Sherwood, Nichola, Brown, Lynne, Chandler, Ben, Deighton, Kerry, Emma, Temlett, Haunch, Kirsty, Cheeseman, Michelle, Dent, Kathy, Garg, Sanjeev, Gray, Carol, Hood, Marion, Jones, Dawn, Juj, Joanne, Rao, Roshan, Walker, Tara, Al Anizi, Mashel, Cheah, Clarissa, Cheing, Yushio, Coutinho, Francisco, Gondo, Prisca, Hadebe, Bernard, Onie Hove, Mazvangu, khader, Ahamed, Krishnachetty, Bobby, Rhodes, Karen, Sokhi, Jagdish, Baker, Katie-Anne, Bertram, Wendy, Looseley, Alex, Mouton, Ronelle, Arnold, Glenn, Arya, Shobhit, Balfoussia, Danai, Baxter, Linden, Harris, Jame, Jones, Craig, Knaggs, Alison, Markar, Sheraz, Perera, Anisha, Scott, Alasdair, Shida, Asako, Sirha, Ravneet, Wright, Sally, Frost, Victoria, Gray, Catherine, MacGregor, Mark, Andrews, Emma, Arrandale, Lindsay, Barrett, Stephen, Cifra, Elna, Cooper, Mariese, Dragnea, Drago, Elna, Cifra, Maclean, Jennifer, Meier, Sonja, Milliken, Donald, Munns, Christopher, Ratanshi, Nadir, Salvana, Abegail, Watson, Anthony, Ali, Hani, Campbell, Gill, Critchley, Rebecca, Hicks, Catherine, Liddle, Alison, Pass, Marc, Ritchie, Charlotte, Thomas, Charlotte, Too, Lingxi, Welsh, Sarah, Gill, Talvinder, Johnson, Joanne, Reed, Joanne, Davis, Edward, Papadopoullos, Sam, Attwood, Clare, Biffen, Andrew, Boulton, Kerenza, Gray, Sophie, Hay, David, Mills, Sarah, Montgomery, Jane, Riddell, Rory, Simpson, Jame, Bhardwaj, Neeraj, Paul, Elaine, Uwubamwen, Nosakhare, Alexander, Maini, Arrich, Jame, Arumugam, Swarna, Blackwood, Dougla, Boggiano, Victoria, Brown, Robyn, Lam Chan, Yik, Chatterjee, Devnandan, Chhabra, Ashok, Christian, Rachel, Costelloe, Hannah, Coxwell Matthewman, Madeline, Dalton, Emma, Darko, Julia, Davari, Maria, Dave, Tejal, Deacon, Matthew, Deepak, Shantal, Edmond, Holly, Ellis, Jessica, El-Sayed, Ahmed, Eneje, Philip, English, Rose, Ewe, Renee, Foers, William, Franklin, John, Gallego, Laura, Garrett, Emily, Goldberg, Olivia, Goss, Harry, Greaves, Rosanna, Harris, Rudy, Hennings, Charle, Jones, Eleanor, Kamali, Nelson, Kokkinos, Naomi, Lewis, Cary, Lignos, Leda, Malgapo, Evaleen Victoria, Malik, Rizwana, Milne, Andrew, Mulligan, John-Patrick, Nicklin, Philippa, Palipane, Natasha, Parsons, Thoma, Piper, Rebecca, Prakash, Rohan, Ramesh, Byron, Rasip, Sarah, Reading, Jacob, Rela, Mariam, Reyes, Anna, Robert, Stephen, Rooms, Martin, Shah, Karishma, Simons, Henry, Solanki, Shalil, Spowart, Emma, Stevens, Amy, Thomas, Christopher, Waggett, Helena, Yassaee, Arrash, Kennedy, Anthony, Scott, Sara, Somanath, Sameer, Berg, Andrew, Hernandez, Miguel, Nanda, Rajesh, Tank, Ghanshyambhai, Wilson, Natalie, Wilson, Debbie, Al-Soudaine, Yassr, Baldwin, Matthew, Cornish, Julie, Davies, Zoe, Davies, Leigh, Edwards, Marc, Frewer, Natasha, Gallard, Sian, Glasbey, Jame, Harries, Rhiannon, Hopkins, Luke, Kim, Taeyang, Koompirochana, Vilavan, Lawson, Simon, Lewis, Megan, Makzal, Zaid, Scourfield, Sarah, Ahmad, Yousra, Bates, Sarah, Blackwell, Clare, Bryant, Helen, Coulter, Suzanne, Cruickshank, Ro, Daniel, Sonya, Daubeny, Thoma, Edwards, Mark, Golder, Kim, Hawkins, Lesley, Helen, Bryant, Hinxman, Honor, Levett, Denny, Skinner, Ben, Walsgrove, Joseph, Dickson, Jane, Constantin, Kathryn, Karen, Markwell, O’Brien, Peter, O’Donohoe, Lynn, Payne, Hannah, Sundayi, Saul, Walker, Elaine, Brooke, Jenny, Cardy, Jon, Humphreys, Sally, Kessack, Laura, Kubitzek, Christiane, Kumar, Suha, Cotterill, Donna, Hodzovic, Emil, Hosdurga, Gurunath, Miles, Edward, Saunders, Glenn, Campbell, Marta, Chan, Peter, Jemmett, Kim, Raj, Ashok, Naik, Aditi, Ramamoorthy, Rajarajan, Shah, Nimesh, Sylvan, Axel, Blyth, Katharine, Burtenshaw, Andrew, Freeman, David, Johnson, Emily, Lo, Philip, Martin, Terry, Plunkett, Emma, Wollaston, Julie, Allison, Joanna, Carroll, Christine, Craw, Nichola, Craw, Sarah, Pitt-Kerby, Tressy, Rowland-Axe, Rebecca, Spurdle, Katie, McDonald, Andrew, Simon, Davie, Sinha, Vivek, Smith, Thoma, Banner-Goodspeed, Valerie, Boone, Myle, Campbell, Kathleen, Lu, Fengxin, Scannell, Joseph, Sobol, Julia, Balajonda, Naraida, Clemmons, Karen, Conde, Carlo, Funk, Bonita, Hall, Roger, Hopkins, Thoma, Olaleye, Omowunmi, Omer, Omer, Pender, Michelle, Porto, Angelo, Stevens, Alice, Waweru, Peter, Yeh, Erlinda, Bodansky, Daniella, Evans, Adam, Kleopoulos, Steven, Maril, Robert, Mathney, Edward, Sanchez, Angela, Tinuoye, Elizabeth, Bateman, Brian, Eng, Kristen, Jiang, Ning, Ladha, Karim, Needleman, Joseph, Chen, Lee-lynn, Lane, Rondall, Robinowitz, David, Ghushe, Neil, Irshad, Mariam, Patel, Samir, Takemoto, Steven, Wallace, Art, Mazzeffi, Michael, Rock, Peter, Wallace, Karin, Zhu, Xiaomao, Chua, 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A., Klarin, B., Ögren, K., Barras, J.P., Bührer, T., Despotidis, V., Helmy, N., Holliger, S., Raptis, D.A., Schmid, R., Meyer, A., Jaquet, Y., Kessler, U., Muradbegovic, M., Nahum, S.R., Rotunno, T., Schiltz, B., Voruz, F., Worreth, M., Christoforidis, D., Popeskou, S.G., Furrer, M., Prevost, G.A., Stocker, A., Lang, K., Breitenstein, S., Ganter, M.T., Geisen, M., Soll, C., Korkmaz, M., Lubach, I., Schmitz, M., Meyer Zu Schwabedissen, M., Zingg, U., Hillermann, T., Wildi, S., Pinto, B.B., Walder, B., Hübner, M., Mariotti, G., Slankamenac, K., Namuyuga, M., Kyomugisha, E., Kituuka, O., Wesonga Shikanda, A., Kakembo, N., Otim Tom, C., Webombesa, A., Bua, E., Ssettabi, E.M., Epodoi, J., Kabagenyi, F., Kirya, F., Dempsey, G., Seasman, C., Basit Nawaz Khan, R., Kurasz, C., Macgregor, M., Shawki, B., Hariharan, V., Chau, S., Ellis, K., Butt, G., Chicken, D.W., Christmas, N., Allen, S., Daniel, G.D., Dempster, A., Kemp, J., Matthews, L., Mcglone, P., Tambellini, J., Trodd, D., Freitas, K., 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R., Gill, S., Lindley, K., Lklouk, M., Lowery, T., Martin, O., Milne, D., O'Connor, P., Ratcliffe, A., Rose, A., Smith, A., Varma, S., Ward, J., Barcraft-Barnes, H., Camsooksai, J., Colvin, C., Reschreiter, H., Tbaily, L., Venner, N., Hamilton, C., Kelly, L., Toth-Tarsoly, P., Dodsworth, K., Foord, D., Gordon, P., Hawes, E., Lamb, N., Mouland, J., Nightingale, J., Rose, S., Schrieber, J., Al 'Amri, K., Aladin, H., Arshad, M.A., Barraclough, J., Bentley, C., Bergin, C., Carrera, R., Clarkson, A., Collins, M., Denham, S., Griffiths, E., Ip, P., Jeyanthan, S., Joory, K., Kaur, S., Marriott, P., Mitchell, N., Nagaiah, S., Nilsson, A., Parekh, N., Pope, M., Seager, J., Serag, H., Tameem, A., Thomas, A., Thunder, J., Torrance, A., Vohra, R., Whitehouse, A., Wong, T., Blunt, M., Wong, K., Giles, J., Reed, I., Weller, D., Bell, G., Birch, J., Damant, R., Maiden, J., Mewies, C., Prince, C., Radford, J., Balain, B., Banerjee, R., Barnett, A., Burston, B., Edwards, J., Evans, C., Ford, D., Gallacher, P., Hill, S., Jaffray, D., Karlakki, S., Kennedy, J., Kiely, N., Lewthwaite, S., Marquis, C., Ockendon, M., Phillips, S., Pickard, S., Richardson, J., Roach, R., Smith, T., Spencer-Jones, R., Steele, N., Steen, J., Van Liefland, M., White, S., Faulds, M., Harris, M., Nicol, S., Pearson, S.A., Chukkambotla, S., Andrew, A., Attrill, E., Campbell, G., Datson, A., Fouracres, A., Graterol, J., Graves, L., Hong, B., Ishimaru, A., Karthikeyan, A., King, H., Lawson, T., Lee, G., Lyons, S., Macalister Hall, A., Mathoulin, S., Mcintyre, E., Mclaughlin, D., Mulcahy, K., Robbins, J., Sung, W., Tayo, A., Trembath, L., Venugopal, S., Wigmore, G., Boereboom, C., Downes, C., Humphries, R., Melbourne, S., Tou, S., Ullah, S., Batchelor, N., Boxall, L., Broomby, R., Deen, T., Hellewell, A., Helliwell, L., Hutchings, M., Hutchins, D., Keenan, S., Mackie, D., Donna, A., Smith, F., Stone, L., Thorpe, K., Wassall, R., Woodgate, A., Baillie, S., Campbell, T., James, S., King, C., Marques de Araujo, D., Martin, D., Morkane, C., Neely, J., Rajendram, R., Burton, M., James, K., Keevil, E., Minik, O., Morgan, J., Musgrave, A., Rajanna, H., Roberts, T., Adamson, M., Jumbe, S., Kendall, J., Muthuswamy, M.B., Cruikshanks, A., Wrench, I., Zeidan, L., Ardern, D., Harris, B., Hellstrom, J., Martin, J., Thomas, R., Varsani, N., Wrey Brown, C., Docherty, P., Gillies, M., McGregor, E., Usher, H., Craig, J., Ahmad, T., Bodger, P., Creary, T., Fowler, A., Ijuo, E., Jones, T., Kantsedikas, I., Lahiri, S., McLean, A.L., Niebrzegowska, E., Phull, M., Wickboldt, N., Baldwin, J., Doyle, D., Mcmullan, S., Oladapo, M., Owen, T., Williams, A., Gregory, P., Husain, T., Kirk-Bayley, J., Mathers, E., Montague, L., Avis, J., Cook, T., Dali-Kemmery, L., Kerslake, I., Lambourne, V., Pearson, A., Boyd, C., Callaghan, M., Lawson, C., McCrossan, R., Nesbitt, V., O'connor, L., Sinclair, R., Farid, N., Morgese, C., Bhatia, K., Karmarkar, S., Ahmed, J., Branagan, G., Hutton, M., Swain, A., Brookes, J., Cornell, J., Dolan, R., Hulme, J., Jansen van Vuuren, A., Jowitt, T., Kalashetty, G., Lloyd, F., Patel, K., Sherwood, N., Brown, L., Chandler, B., Deighton, K., Emma, T., Haunch, K., Cheeseman, M., Dent, K., Gray, C., Hood, M., Jones, D., Juj, J., Rao, R., Walker, T., Al Anizi, M., Cheah, C., Cheing, Y., Coutinho, F., Gondo, P., Hadebe, B., Onie Hove, M., Khader, A., Krishnachetty, B., Rhodes, K., Sokhi, J., Baker, K.A., Bertram, W., Looseley, A., Mouton, R., Arnold, G., Arya, S., Balfoussia, D., Baxter, L., Harris, J., Jones, C., Knaggs, A., Markar, S., Perera, A., Scott, A., Shida, A., Sirha, R., Wright, S., Frost, V., MacGregor, M., Andrews, E., Arrandale, L., Barrett, S., Cifra, E., Cooper, M., Dragnea, D., Elna, C., Maclean, J., Meier, S., Milliken, D., Munns, C., Ratanshi, N., Salvana, A., Watson, A., Ali, H., Critchley, R., Hicks, C., Liddle, A., Pass, M., Ritchie, C., Thomas, C., Too, L., Welsh, S., Gill, T., Johnson, J., Reed, J., Davis, E., Papadopoullos, S., Attwood, C., Biffen, A., Boulton, K., Gray, S., Hay, D., Mills, S., Montgomery, J., Riddell, R., Simpson, J., Bhardwaj, N., Paul, E., Uwubamwen, N., Alexander, M., Arrich, J., Arumugam, S., Blackwood, D., Boggiano, V., Lam Chan, Y., Chatterjee, D., Chhabra, A., Christian, R., Costelloe, H., Coxwell Matthewman, M., Dalton, E., Darko, J., Davari, M., Dave, T., Deacon, M., Deepak, S., Edmond, H., Ellis, J., El-Sayed, A., Eneje, P., English, R., Ewe, R., Foers, W., Franklin, J., Gallego, L., Garrett, E., Goldberg, O., Goss, H., Greaves, R., Harris, R., Hennings, C., Jones, E., Kamali, N., Kokkinos, N., Lewis, C., Lignos, L., Malgapo, E.V., Malik, R., Milne, A., Mulligan, J.P., Nicklin, P., Palipane, N., Parsons, T., Piper, R., Prakash, R., Ramesh, B., Rasip, S., Reading, J., Rela, M., Reyes, A., Robert, S., Rooms, M., Shah, K., Simons, H., Solanki, S., Spowart, E., Stevens, A., Waggett, H., Yassaee, A., Kennedy, A., Scott, S., Somanath, S., Berg, A., Hernandez, M., Nanda, R., Tank, G., Wilson, N., Wilson, D., Al-Soudaine, Y., Baldwin, M., Cornish, J., Davies, Z., Davies, L., Edwards, M., Frewer, N., Gallard, S., Glasbey, J., Harries, R., Hopkins, L., Kim, T., Koompirochana, V., Lawson, S., Lewis, M., Makzal, Z., Scourfield, S., Ahmad, Y., Bates, S., Blackwell, C., Bryant, H., Coulter, S., Cruickshank, R., Daniel, S., Daubeny, T., Golder, K., Hawkins, L., Helen, B., Hinxman, H., Levett, D., Skinner, B., Walsgrove, J., Dickson, J., Constantin, K., Karen, M., O'Brien, P., O'Donohoe, L., Payne, H., Sundayi, S., Walker, E., Brooke, J., Cardy, J., Humphreys, S., Kessack, L., Kubitzek, C., Kumar, S., Cotterill, D., Hodzovic, E., Hosdurga, G., Miles, E., Saunders, G., Campbell, M., Chan, P., Jemmett, K., Raj, A., Naik, A., Ramamoorthy, R., Shah, N., Sylvan, A., Blyth, K., Burtenshaw, A., Freeman, D., Johnson, E., Lo, P., Martin, T., Plunkett, E., Wollaston, J., Allison, J., Carroll, C., Craw, N., Craw, S., Pitt-Kerby, T., Rowland-Axe, R., Spurdle, K., McDonald, A., Simon, D., Sinha, V., Banner-Goodspeed, V., Boone, M., Campbell, K., Lu, F., Scannell, J., Sobol, J., Balajonda, N., Clemmons, K., Conde, C., Funk, B., Hopkins, T., Olaleye, O., Omer, O., Pender, M., Porto, A., Waweru, P., Yeh, E., Bodansky, D., Evans, A., Kleopoulos, S., Maril, R., Mathney, E., Sanchez, A., Tinuoye, E., Bateman, B., Eng, K., Jiang, N., Ladha, K., Needleman, J., Chen, L.L., Lane, R., Robinowitz, D., Ghushe, N., Irshad, M., Patel, S., Takemoto, S., Wallace, A., Mazzeffi, M., Rock, P., Wallace, K., Zhu, X., Chua, P., Mattera, M., Sharar, R., Thilen, S., Treggiari, M., Morgan, A., Sofjan, I., Subramaniam, K., Avidan, M., Maybrier, H., Muench, M., and Wildes, T.
Subjects: Male, HSJ UCI, Critical Care and Intensive Care Medicine, law.invention, Perioperative Care/methods, 0302 clinical medicine, Surgical procedures, 030202 anesthesiology, law, Critical care/utilisation, Postoperative care/methods, Postoperative care/statistics and numerical data, Surgical procedures, operative/mortality, statistics and numerical data, Prospective Studies, Postoperative Period, Postoperative care/methods, education.field_of_study, Postoperative care/method, Elective Surgical Procedures/mortality, fluid output, Middle Aged, fluid administration, Intensive care unit, Hospitalization, Length of Stay/statistics & numerical data, operative/mortality, Intensive Care Units/statistics & numerical data, outcome, Female, Elective Surgical Procedure, Human, Adult, medicine.medical_specialty, Logistic Model, Postoperative care/statistics and numerical data, Critical care/utilisation, Population, Intensive Care Unit, Elective Surgical Procedures/statistics & numerical data, Hospitalization/statistics & numerical data, Humans, Logistic Models, Surgical procedures, operative/mortality, Postoperative care, methods, Perioperative Care, NO, 03 medical and health sciences, Anesthesiology, Intensive care, medicine, Elective surgery, Intensive care medicine, education, business.industry, 030208 emergency & critical care medicine, Perioperative, Length of Stay, Clinical trial, Prospective Studie, septic shock, business
Abstract: PURPOSE: As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality. METHODS: Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests. RESULTS: 44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10-5.21]; p < 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings. CONCLUSIONS: We did not identify any survival benefit from critical care admission following surgery. info:eu-repo/semantics/publishedVersion
Published: 2017
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46. The Reproducibility of the Point of Care Microcirculation (POEM) Score When Used to Assess Critically Ill Patients: A Multicenter Prospective Observational Study

Author: Jakob Wollborn, Ulrich Goebel, Muhammad Gilani, Hithem Fargaly, James Watchorn, Andrew R. Deitchman, Sam Hutchings, David N. Naumann, Michael T. McCurdy, and Jordan Assadi
Subjects: Ordinal data, Male, medicine.medical_specialty, Blinding, Critical Illness, Video microscopy, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Cohen's kappa, Medicine, Humans, Prospective Studies, CLIPS, Reliability (statistics), Point of care, computer.programming_language, Microscopy, Video, business.industry, Microcirculation, Reproducibility of Results, 030208 emergency & critical care medicine, Middle Aged, Point-of-Care Testing, Emergency Medicine, Physical therapy, Observational study, Female, business, computer
Abstract: Background The current standard of analyzing microcirculatory video microscopy is time-consuming and occurs away from the patient, limiting its clinical utility. Point-of-care assessment with incident dark field (IDF) microscopy, however, may offer greater clinical applicability. We aimed to determine the reproducibility of the Point of Care Microcirculation (POEM) tool when used at the bedside in critically ill patients. Methods A multinational, multicenter, prospective observational study of adult intubated patients was undertaken during a 9-month period in Germany, the United Kingdom, and the United States. A user recorded a batch of four standardized video clips from each patient, calculated a POEM score and recorded the time for image acquisition. A second user blinded to the first repeated this process. Patients with video clips of poor quality were excluded. At a later date, the two users again blinded themselves to reassess both their own clips and those of the other user. Basic demographic information was recorded. Intrauser reliability (an individual user rescoring the same batch of videos after blinding), interuser reliability (a second user rescoring the other user's video batch after blinding), and test-retest reliability (two users individually capturing videos and recording POEM scores) were assessed using a linearly weighted kappa statistic for ordinal data. Results Sixty-five patients were included in the final analysis. Observer agreement was substantial for all tests. Intrauser agreement was 0.73 (0.95 CI 0.64-0.81), interuser agreement 0.71 (0.95 CI 0.63-0.79), and test-retest agreement 0.75 (0.95 CI 0.65-0.86). Average time to record videos and assess POEM scores 7:34 ± 3:37 minutes. Conclusions Point-of-care assessment of the microcirculation using IDF video microscopy and POEM scoring appears to be both a feasible and reproducible approach to microcirculatory assessment. Testing of the score in critically ill patients showed substantial agreement within and between investigators, but further studies should validate its utility as a tool to guide shock resuscitation.
Published: 2019

47. Argon reduces microglia activation and ramification dependent inflammatory cytokine expression in the retina

Author: Sashko Spassov, Stefanie Scheid, Ulrich Goebel, Hartmut Buerkle, Nils Schallner, Jakob Wollborn, and Felix Ulbrich
Subjects: Retina, medicine.anatomical_structure, Microglia, Chemistry, Ramification (botany), medicine, Cytokine expression, Cell biology
Abstract: Background: Perioperative damage of neuronal tissue due to insufficient cerebral circulation as a result of hypotension or stroke, lead to permanent destruction and functional impairment via apoptotic and inflammatory pathways. Recently, the noble gas argon has been shown to exert neuroprotective effects. Despite intensive research, the exact mechanism remains unclear. Methods: In-vitro, after injury of human neuroblastoma cells with rotenone over a period of four hours, postconditioning with argon 75 Vol% was performed for 2. In-vivo, retinal ischemia reperfusion injury in the rat was induced by increasing intraocular pressure for 1 hour (h). Upon reperfusion, argon was administered by inhalation for 2 h. Results: In summary, argon reduced binding activity of transcription factors involved in regulation of neuronal damage such as STAT3 (Signal transducer and activator of transcription 3), NF-kB (Nuclear factor `kappa-light-chain-enhancer´ of activated B-cells), AP-1 (Activator protein 1) and Nrf-2 (Nuclear factor erythroid 2-related factor 2). Flow cytometry analysis showed that argon down-regulated the Fas-Ligand. Since some of these transcription factors were regulated via toll-like receptors (TLR), their effects could be eliminated - at least in part - by OxPAPC (TLR2 and -4 inhibitor). Argon was able to reduce the quantity and the activity of neuronal microglia after ischemia-reperfusion injury. Consecutively, qPCR (quantitative Polymerase chain reaction) showed a reduction of the pro-inflammatory cytokines IL-1α (Interleukin-1α), IL-1ß (Interleukin-1ß), IL-6 (Interleukin 6), TNFα (Tumor necrosis factor alpha) and iNOS (inducible Nitric oxide synthase). Conclusion: Argon reduced the extent of inflammation after neuronal injury by suppression of transcription factors crucial for microglia activation. The therapeutic use of the noble gas would be ideal for treating in the context of neuronal damage due to the lack of known side effects and narcotic properties with preservation of neurological assessability. Although preclinical studies are promising, further investigations are required before argon can be approved for use in patients.
Published: 2019
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48. LMA Gastro™ airway is feasible during upper gastrointestinal interventional endoscopic procedures in high risk patients: a single-center observational study

Author: Axel Schmutz, Thomas Loeffler, Arthur Schmidt, and Ulrich Goebel
Subjects: Adult, Male, Risk, Endoscopic procedures, Achalasia, High-risk patients, Equipment Design, Anesthesia, General, Middle Aged, Endoscopic submucosal dissection, digestive system diseases, Endoscopy, Gastrointestinal, Laryngeal Masks, lcsh:RD78.3-87.3, Cohort Studies, lcsh:Anesthesiology, Supraglottic airway device, Feasibility Studies, Humans, Female, Aged, Retrospective Studies, Research Article
Abstract: Background Nonoperating room anesthesia during gastroenterological procedures is a growing field in anesthetic practice. While the numbers of patients with severe comorbidities are rising constantly, gastrointestinal endoscopic interventions are moving closer to minimally invasive endoscopic surgery. The LMA Gastro™ is a new supraglottic airway device, developed specifically for upper gastrointestinal endoscopy and interventions. The aim of this study was to evaluate the feasibility of LMA Gastro™ in patients with ASA physical status ≥3 undergoing advanced endoscopic procedures. Methods We analyzed data from 214 patients retrospectively who received anesthesia for gastroenterological interventions. Inclusion criteria were upper gastrointestinal endoscopic interventions, airway management with LMA Gastro™ and ASA status ≥3. The primary outcome measure was successful use of LMA Gastro™ for airway management and endoscopic intervention. Results Thirtyone patients with ASA physical status ≥3, undergoing complex and prolonged upper gastrointestinal endoscopic procedures were included. There were 7 endoscopic retrograde cholangiopancreatographies, 7 peroral endoscopic myotomies, 5 percutaneous endoscopic gastrostomies and 12 other complex procedures (e.g. endoscopic submucosal dissection, esophageal stent placement etc.). Of these, 27 patients were managed successfully using the LMA Gastro™. Placement of the LMA Gastro™ was reported as easy. Positive pressure ventilation was performed without difficulty. The feasibility of the LMA Gastro™ for endoscopic intervention was rated excellent by the endoscopists. In four patients, placement or ventilation with LMA Gastro™ was not possible. Conclusions We demonstrated the feasibility of the LMA Gastro™ during general anesthesia for advanced endoscopic procedures in high-risk patients. Trial registration German Clinical Trials Register ( DRKS00017396 ) Date of registration: 23rd May 2019, retrospectively registered.
Published: 2019

49. Comparison of airway management techniques for different access in a simulated motor vehicle entrapment scenario

Author: Ulrich Goebel, Daniel Steinmann, Thomas Ahne, and C. Heringhaus
Subjects: Adult, Laryngeal tube, Emergency Medical Services, Engineering, medicine.medical_treatment, Context (language use), Laryngoscopes, Manikins, Airtraq, Laryngeal Masks, 03 medical and health sciences, 0302 clinical medicine, Laryngeal mask airway, 030202 anesthesiology, Intubation, Intratracheal, medicine, Humans, Intubation, Airway Management, business.industry, Accidents, Traffic, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Emergency Medical Technicians, Anesthesia, Emergency Medicine, Airway management, Medical emergency, Advanced airway management, business, Airway
Abstract: BACKGROUND Emergency airway management can be particularly challenging in patients entrapped in crashed cars because of limited access. The aim of this study was to analyse the feasibility of four different airway devices in various standardized settings utilized by paramedics and emergency physicians. METHODS Twenty-five paramedics and 25 emergency physicians were asked to perform advanced airway management in a manikin entrapped in a car's left front seat, with access to the patient through the opened driver's door or access from the back seat. Available airway devices included Macintosh and Airtraq laryngoscopes, as well as laryngeal mask airway (LMA) Supreme and the Laryngeal Tube. The primary endpoints were successful placement, along with attempts needed to do so, and time for successful placement. The secondary endpoints included Cormack-Lehane grades and rating of the difficulty of the technique with the different devices. RESULTS The overall intubation and placement success rates were equal for the Macintosh and Airtraq laryngoscopes as well as the LMA Supreme and Laryngeal Tube, with access from the back seat being superior in terms of placement time and ease of use. Supraglottic airway devices required half of the placement time and were easier to use compared with endotracheal tubes (with placement times almost >30 s). Paramedics and emergency physicians achieved equal overall successful placement rates for all devices. CONCLUSION Both scenarios of securing the airway seem suitable in this manikin study, with access from the back seat being superior. Although all airway devices were applicable by both groups, paramedics and emergency physicians, supraglottic device placement was faster and always possible at the first attempt. Therefore, the LMA Supreme and the Laryngeal Tube are attractive alternatives for airway management in this context if endotracheal tube placement fails. Furthermore, supraglottic device placement, while the patient is still in the vehicle, followed by a definitive airway once the patient is extricated would be a worthwhile alternative course of action.
Published: 2016
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50. Carbon monoxide treatment reduces microglial activation in the ischemic rat retina

Author: Ulrich Goebel, Daniel Böhringer, Petar Charalambous, Felix Ulbrich, Julia Biermann, and Wolf A. Lagrèze
Subjects: Male, Retinal Ganglion Cells, 0301 basic medicine, Retinal degeneration, medicine.medical_specialty, Retinal ganglion, Rats, Sprague-Dawley, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Animals, Fluorescent Antibody Technique, Indirect, Neuroinflammation, Carbon Monoxide, Retina, Blood Cells, Microglia, Chemistry, Calcium-Binding Proteins, Microfilament Proteins, Retinal Degeneration, Retinal Vessels, Retinal, medicine.disease, Sensory Systems, Rats, Disease Models, Animal, Ophthalmology, Neuroprotective Agents, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Retinal ganglion cell, Reperfusion Injury, Anesthesia, Female, Reperfusion injury, 030217 neurology & neurosurgery
Abstract: Ischemia and reperfusion (I/R) injury damages retinal neurons. Retinal injury is accompanied by activation of microglia, which scavenge the dead or dying neurons, but increasing evidence now indicates that amoeboid-shaped microglia cells activated in the brain after ischemia have neurotoxic and damaging properties in their own right. A previous study showed that postconditioning with carbon monoxide (CO) protects retinal ganglion cells (RGCs) after I/R through anti-apoptotic and anti-inflammatory mechanisms. The present study was designed to investigate and quantify the activation of retinal microglia after I/R with and without CO postconditioning. Adult Sprague–Dawley rats underwent retinal ischemia by increasing the ocular pressure to 120 mmHg for 1 h through a needle inserted into the anterior chamber. Reperfusion was induced by removing the needle. After I/R, one group of animals was kept in a CO (250 ppm) atmosphere for 1 h; the other group was kept in room air (Air). At 1, 2, 3, and 7 days after I/R, the eyes were enucleated and fixed. Intracardiac blood was analyzed for systemic effects of CO or I/R. Retinal cross sections were taken from the middle third of the eye and were stained with anti-Iba-1. Microglia cells were graded as amoeboid or ramified phenotypes according to morphologic criteria. Retinal thicknesses were determined. Evaluation of retinal tissue revealed a significant reduction of amoeboid microglia cells after I/R + CO when compared to the I/R + Air group. The peak number of amoeboid microglia was observed at day 2 post-I/R + Air. This rise was attenuated by CO postconditioning (815 versus 572 cells/mm2 for I/R + Air versus I/R + CO, respectively; p = 0.005). CO reduced and further postponed the peak in the numbers of amoeboid and ramified microglia cells in ischemic eyes and prevented microglial activation in the contralateral eyes. I/R-induced leucocytosis was inhibited by CO inhalation. The reduction of retinal thickness after I/R was more serious after Air inhalation when compared to the CO group. Numerous activated microglia cells appear in the inner retina after I/R, and CO-treatment significantly attenuates this glial response. Antagonism of microglial activation may be a further neuroprotective effect of CO, apart from its direct anti-apoptotic capacity.
Published: 2016
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