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2. Real-life evaluation of NIV to CPAP switch in patients with chronic respiratory failure. A case control study

Author

Louise Mathieu, Claudio Rabec, Guillaume Beltramo, Ludwig S. Aho, Pierre Tankere, Déborah Schenesse, Jade Chorvoz, Philippe Bonniaud, and Marjolaine Georges

Abstract

Background Non-invasive ventilation (NIV) is a standard of care for hypercapnic chronic respiratory failure (CRF). Obstructive sleep apnea (OSA) frequently contribute to hypoventilation in CRF. CPAP improves hypercapnia in selected COPD and obese patients. We describe the profile of patients switching from NIV to CPAP in a cohort of patients on long-term NIV and identify factors associated with a successful switch. Methods The observational research protocol evaluation committee of the French Pneumology Society approved this case-control study (CEPRO 2022-015). We compared 88 consecutive candidates for a NIV-CPAP switch with 266 controls among 394 ventilated patients treated at the Dijon University Hospital between 2015 and 2020. They followed a standardized protocol including a poly(somno)graphy recorded after NIV withdrawal for three nights. CPAP trial was performed if severe OSA was confirmed. Recurrent hypoventilation was checked after one night and one month under CPAP. Results Patients were 53% males, median age 65 [56–74] years, and median BMI 34 [25-38.5] kg/m2. Sixty seven percent of patients were safely switched and remained on CPAP. The probability of a NIV-CPAP switch was correlated to older age (OR:1.3 [1.01–1.06]), CRF etiology (OR for COPD:20.37 [4.2–98,72], obesity:7.31 [1.58–33.74]), circumstances of NIV initiation (OR for acute exacerbation:11.64 [2.03–66.62]), lower pressure support (OR:0.90 [0.73–0.92]), lower baseline PaCO2 (OR:0.85 [0.80–0.91]) and lower compliance (OR:0.76 [0.64–0.90]). Pressure support level was the only factor associated with the outcome of the NIV-CPAP switch. Conclusions A NIV-CPAP switch is possible in real life conditions in stable obese and COPD patients with underlying OSA.

Published
2023
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3. Discrimination and sexual harassment – Results from the largest German medical university

Author

Ludwig, S., Jenner, S., Berger, R., Tappert, S., Kurmeyer, C., Oertelt-Prigione, Sabine, and Petzold, M.

Subjects
Public Health, Environmental and Occupational Health
Abstract

Background Discrimination and sexual harassment in the workplace and in higher education institutions are important public health issues. Here we aim at analyzing the prevalence of discrimination and sexual harassment of lecturers and students at one of the largest teaching hospitals in Europe. We assess whether there are differences between lecturers and students, women and men, and different study programs. Methods An online questionnaire was sent to N = 7095 students of all study programs and N = 2528 lecturers at Charité - Universitätsmedizin Berlin. The survey was conducted from November 2018 to February 2019. We investigated experienced or observed discrimination or sexual harassment at the medical faculty. Furthermore, we analyzed frequency, perpetrators, situational factors, attributed reasons and forms of harassment encountered. Results A total of 964 (14%) students (S) and 275 (11%) of lecturers (L) participated in the survey. Discriminatory behavior was witnessed and/or experienced by 49,6% of students (L: 31%), sexual harassment by 23,6% of students (L: 19,2%). Students state lecturers (85,9%) as main source of discriminatory behavior (L: directors/supervisors: 47,4%; students 41,0%). Sex/Gender (S: 71%; L: 60,3%) is cited most frequently as reason for discriminatory experiences. Female students and faculty experience more discrimination and sexual harassment. Conclusions Discrimination and sexual harassment are prevalent in academic medicine. There are differences in the reasons and sources of discrimination and sexual harassment between students and lecturers. Specific programs for lecturers and students are necessary to educate the faculty on how to prevent and respond to it and whom to address. Key messages • National preventive strategies should be implemented to tackle issues of discrimination and harassment in higher education institutions. • Special attention should be paid to female students and lecturers.

Published
2022
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4. Antiplatelet and anticoagulant agents in vitreoretinal surgery: a prospective multicenter study involving 804 patients

Author

Meillon, Cyril, Gabrielle, Pierre Henry, Luu, Maxime, Aho-Glélé, Ludwig S., Bron, Alain, Creuzot Garcher, Catherine, Department of Ophthalmology, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
anticoagulants, antithrombotic therapy, vitreoretinal surgery, Sensory Systems, 3. Good health, 03 medical and health sciences, Cellular and Molecular Neuroscience, Ophthalmology, 0302 clinical medicine, 030221 ophthalmology & optometry, antiplatelets agents, 030212 general & internal medicine, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Publication for the CFSR Research Net; PURPOSE: To assess the rate of hemorrhagic complications after vitreoretinal surgery and the influence of antithrombotic agents. METHODS: Hemorrhagic complications of vitreoretinal procedures performed in seven ophthalmologic centers on patients treated or not treated with antiplatelet (AP) or anticoagulant (AC) agents were prospectively collected. Patients' characteristics, surgical techniques, and complications were recorded during surgery and for 1 month after. RESULTS: Eight hundred four procedures were performed between January 2015 and April 2015. Among them, 18.4% were treated with AP agents (n = 148) and 7.8% with AC agents (n = 63), with 18 of them treated with NOACS (new oral anticoagulants). AP or AC agents were continued in 96.5% and 80.7% of cases, respectively. Fifty-three patients (6.6%) developed one or more hemorrhagic complications in one eye during this period. In univariate analysis, AC agents were not associated with hemorrhagic complications (P = 0.329) in contrast to AP (P = 0.005). However, in multivariate analysis, AP agents were no longer associated with hemorrhagic complications and the intraoperative use of endodiathermy was the only factor associated with hemorrhagic complications (P = 0.001). CONCLUSIONS: This study showed that AP and AC agents were not a factor associated with hemorrhagic complications during vitreoretinal surgery. The continuation of these treatments should be considered without risk of severe hemorrhagic complications.

Published
2018
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5. A spiking neuron implementation of genetic algorithms for optimization

Author

Ludwig, S., Hartjes, J., Pol, B., Rivas, G., Kwisthout, J.H.P., Cao, L., Kosters, W., Lijffijt, J., Cao, L., Kosters, W., and Lijffijt, J.

Subjects
Cognitive artificial intelligence
Abstract

Item does not contain fulltext BNAIC'20: 32nd Benelux Conference on AI (Leiden, the Netherlands, 19-20 November 2020)

Published
2020

6. Role of Power Distribution System Tests in Final Assembly of a Military Derivative Airplane

Author

Ludwig S. Donaty, Timothy W. Matthews, Kenneth M. Milburn, Kevin K. Chang, and K. Paul Hemmaplardh

Subjects
Distribution system, Engineering, chemistry.chemical_compound, business.product_category, chemistry, business.industry, Aerospace Engineering, Mechanical engineering, Structural engineering, business, Derivative (chemistry), Airplane, Power (physics)
Published
2009
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7. Regional Adoption of Business-to-Business Electronic Commerce in China: Role of E-Readiness

Author

Tan, D.J. and Ludwig, S.

Subjects
B2B e-commerce adoption, Internet-based EDI, developing country, PERM, inter-organizational relationships, economic-cultural context
Abstract

Adoption of B2B e-commerce is a powerful driver of economic success in developed and developing countries. However, adoption rates in developing countries lag far behind. This paper draws on the Perceived eReadiness Model and research on the influence of inter-organizational relationships and economic-cultural contexts to explain the importance of three factors—inter-organizational power dependence, cooperativeness, and regional economic-cultural differences—for achieving higher levels of Internet-based Electronic Data Interchange (EDI) in the developing country of China. We employ survey data to empirically test both the individual and joint influence of these factors. The findings suggest that beyond intra-organizational and external factors, managers and policy makers wanting to promote Internet-based EDI adoption in developing countries must also account for the inter-organizational relationships of firms and the economic and cultural circumstances of the regions in which they operate.

Published
2016
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8. Somatosensorisch evozierte Potenziale und biochemische Marker neuronaler Defizite während Endarterektomie der A. carotis in Regionalanästhesie

Author

Ludwig S, Hachenberg T, Christine E. Schneemilch, Ulrich A, and Halloul Z

Subjects
business.industry, medicine.medical_treatment, Perioperative, Brain damage, Carotid endarterectomy, medicine.disease, Hemiparesis, Somatosensory evoked potential, Anesthesia, medicine, Arterial blood, Surgery, General anaesthesia, medicine.symptom, business, Stroke
Abstract

OBJECTIVE OF THE STUDY: Carotid endarterectomy (CEA) remains the standard procedure for primary and secondary prevention of stroke. Somato-sensory evoked potentials (SEP) are frequently used in carotid endarterectomy under general anaesthesia and recommended for monitoring cerebral functions. The aim of the study was to compare changes in SEP and serum levels of S-100 beta protein and neuron-specific enolase (NSE) with perioperative clinical neurological deficits in patients undergoing regional anaesthesia (RA). PATIENTS AND METHODS: After approval of the ethics committee of the Otto-von-Guericke-University, Magdeburg fifty patients undergoing elective CEA under RA were prospectively investigated. RA was performed by combined deep and superficial cervical plexus blockade. SEP was monitored continuously during the surgical procedure. A more of 50 % decrease of potentials (N 20 / P 25 amplitude) compared to potentials before clamping was considered to be significant. Arterial blood samples were collected preoperatively, before declamping and on the first postoperative day to determine serum levels of S-100 beta and NSE. RESULTS: 12 patients developed intraoperatively neurological deficits with carotid clamping. The symptoms were transient and regressed in one minute after shunting. One patient was discharged with persistent hemiparesis. In 8 of 12 patients (66 %) with neurological deficits a more of 50 % decrease of potentials was observed. In one patient with loss of consciousness and hemiparesis changes in SEP or decrease in N 20 / P 25 amplitude were absent. Decrease in amplitude was in patients with intraoperative neurological deficits with 78 % versus 34 % in patients without any deficits significantly reduced (p = 0.01). The sensitivity of monitoring was 67 % at a specifity of 74 %. Serum levels of S-100 beta increased before declamping between patients with and without any neurological deficits significantly (p = 0.02). On the first postoperative day, increased levels of S-100 beta correlated with decrease in amplitude (p = 0.001). CONCLUSION: Compared to SEP, CEA under regional anaesthesia is a safer method to detect patients with cerebral ischaemia before irreversible cellular brain damage occurs. Measuring blood levels of S-100 beta could help to evaluate patients with risk to develop cerebral ischaemia during clamping.

Published
2007
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9. Reply: To PMID 25892127

Author

Denis, Dossarps, Alain M, Bron, Philippe, Koehrer, Ludwig S, Aho-Glélé, and Catherine, Creuzot-Garcher

Subjects
Male, Endophthalmitis, Intravitreal Injections, Visual Acuity, Humans, Female, Eye Infections, Bacterial
Published
2015

10. Towards combined transport and optical studies of the 0.7-anomaly in a quantum point contact

Author

Schubert, E., Heyder, J., Bauer, F., Stumpf, W., Wegscheider, W., Delft, J. v., Ludwig, S., and Högele, A.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Mesoscale and Nanoscale Physics (cond-mat.mes-hall), FOS: Physical sciences
Abstract

A Quantum Point Contact (QPC) causes a one-dimensional constriction on the spatial potential landscape of a two-dimensional electron system. By tuning the voltage applied on a QPC at low temperatures the resulting regular step-like electron conductance quantization can show an additional kink near pinch-off around 0.7(2$e^2$/h), called 0.7-anomaly. In a recent publication, we presented a combination of theoretical calculations and transport measurements that lead to a detailed understanding of the microscopic origin of the 0.7-anomaly. Functional Renormalization Group-based calculations were performed exhibiting the 0.7-anomaly even when no symmetry-breaking external magnetic fields are involved. According to the calculations the electron spin susceptibility is enhanced within a QPC that is tuned in the region of the 0.7-anomaly. Moderate externally applied magnetic fields impose a corresponding enhancement in the spin magnetization. In principle, it should be possible to map out this spin distribution optically by means of the Faraday rotation technique. Here we report the initial steps of an experimental project aimed at realizing such measurements. Simulations were performed on a particularly pre-designed semiconductor heterostructure. Based on the simulation results a sample was built and its basic transport and optical properties were investigated. Finally, we introduce a sample gate design, suitable for combined transport and optical studies.

Published
2014
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11. Magneto-electrical subbands of freely suspended quantum point contacts

Author

Rossler, C., Herz, M., Bichler, M., and Ludwig, S.

Subjects
Condensed Matter - Other Condensed Matter, Condensed Matter - Mesoscale and Nanoscale Physics, Mesoscale and Nanoscale Physics (cond-mat.mes-hall), FOS: Physical sciences, Condensed Matter::Mesoscopic Systems and Quantum Hall Effect, Other Condensed Matter (cond-mat.other)
Abstract

We present a versatile design of freely suspended quantum point contacts with particular large one-dimensional subband quantization energies of up to 10meV. The nanoscale bridges embedding a two-dimensional electron system are fabricated from AlGaAs/GaAs heterostructures by electron-beam lithography and etching techniques. Narrow constrictions define quantum point contacts that are capacitively controlled via local in-plane side gates. Employing transport spectroscopy, we investigate the transition from electrostatic subbands to Landau-quantization in a perpendicular magnetic field. The large subband quantization energies allow us to utilize a wide magnetic field range and thereby observe a large exchange splitted spin-gap of the two lowest Landau-levels.

Published
2009
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12. Asymmetric non-linear response of the IQHE

Author

Siddiki, A., Horas, J., Kupidura, D., Wegscheider, W., and Ludwig, S.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Mesoscale and Nanoscale Physics (cond-mat.mes-hall), FOS: Physical sciences, Condensed Matter::Mesoscopic Systems and Quantum Hall Effect
Abstract

An asymmetric break-down of the integer quantized Hall effect is investigated. This rectification effect is observed as a function of the current value and its direction in conjunction with an asymmetric lateral confinement potential defining the Hall-bar. Our electrostatic definition of the Hall-bar via Schottky-gates allows a systematic control of the steepness of the confinement potential at the edges of the Hall-bar. A softer edge (flatter confinement potential) results in more stable Hall-plateaus, i.e. a break-down at a larger current density. For one soft and one hard edge the break-down current depends on the current direction, resembling rectification. This non-linear magneto-transport effect confirms the predictions of an emerging screening theory of the IQHE., Comment: 4 Pages, 4 Figures

Published
2009
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13. B-type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients

Author

Thomas Münzel, Ludwig S. Weilemann, Felix Post, Christoph Sinning, and Claudia-Martina Messow

Subjects
Male, medicine.medical_specialty, Resuscitation, Critical Care, medicine.drug_class, Ischemia, Context (language use), Critical Care and Intensive Care Medicine, Sepsis, Ventricular Dysfunction, Left, Internal medicine, Intensive care, Natriuretic Peptide, Brain, medicine, Natriuretic peptide, Humans, cardiovascular diseases, Prospective Studies, Intensive care medicine, Aged, Septic shock, business.industry, Models, Cardiovascular, Middle Aged, medicine.disease, Prognosis, Shock, Septic, ROC Curve, Shock (circulatory), Multivariate Analysis, cardiovascular system, Cardiology, Female, medicine.symptom, business, human activities, hormones, hormone substitutes, and hormone antagonists, Biomarkers
Abstract

In early stages of septic shock, impaired myocardial function plays an important prognostic role. In this context, B-type natriuretic peptide (BNP) has been shown to be a neurohumoral marker for left ventricular dysfunction, because myocardial strain and ischemia both increase BNP concentration. The present study was designed to test if BNP allows for identification of patients at risk for developing sepsis-induced myocardial depression and if an increased concentration of BNP is associated with an adverse outcome in patients with septic shock.In a prospective study, 93 patients with septic shock were divided into one group with normal ventricular function (left ventricular ejection fraction50%) on days 3 to 5 (n = 38) and another group of patients with impaired left ventricular function (left ventricular ejection fraction50%) on days 3 to 5 (n = 55). Patients with impaired left ventricular function had an increased median plasma BNP concentration on day 5 (699 [608 of 795.5] pg/nL vs. 86 [71.3 of 93] pg/nL) and an ejection fraction of 38 +/- 6% on day 5 vs. 58 +/- 7% in patients without impaired left ventricular function. There was a close inverse relation between increased plasma BNP concentrations and depressed left ventricular ejection fraction (p0.05). BNP measured at days 3 and 5 revealed an association with the end point of survival. In the proportional hazards regression model adjusted for age, male gender, and creatinine concentration, measured at days 0, 3, 5, and 12, BNP concentration at day 5 showed an increased hazard for reaching the end point (hazard ratio: 1.407; 95% confidence interval: 1.033-1.916; p = 0.030). In an additional receiver operating characteristic curve analysis, the predictive value of a model including cardiovascular risk factors and additional BNP concentration on day 5, compared with a baseline model of cardiovascular risk factors, improved the area under the curve the most; therefore, this model was suited best for prediction of sepsis-induced myocardial depression and 30-day survival for patients with septic shock. Area under the curve of this model combined with BNP concentration at day 5 for death after 30 days (0.65) impaired left ventricular ejection fraction (0.94) and sepsis-induced myocardial depression (0.96).These results indicate that plasma BNP concentration represents a reliable marker for identification of patients developing sepsis-induced myocardial depression. In addition, BNP concentration on day 5 may be used as a prognostic marker to identify patients with an elevated risk for an adverse outcome.

Published
2008

14. Reply

Author

Denis Dossarps, Alain M. Bron, Philippe Koehrer, Ludwig S. Aho-Glélé, and Catherine Creuzot-Garcher

Subjects
03 medical and health sciences, Ophthalmology, 0302 clinical medicine, 010102 general mathematics, 030221 ophthalmology & optometry, 0101 mathematics, 01 natural sciences
Published
2015
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15. Reply

Author

Frcr net, Ludwig S. Aho-Glélé, Alain M. Bron, Denis Dossarps, Philippe Koehrer, and Catherine Creuzot-Garcher

Subjects
Ophthalmology, medicine.medical_specialty, Endophthalmitis, Visual acuity, business.industry, Medicine, medicine.symptom, business, medicine.disease, Surgery
Published
2015
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17. Verzeichnis der Herausgeber und Autoren

Author

Karl-Walter Jauch, Christian Madler, Frank-Gerald Pajonk, Johannes Siegrist, Karl Werdan, Karl-Heinz Altemeyer, Hans-Richard Arntz, Costas Bachtis, Jan Bahr, Rüdiger Baumeister, Thomas Bein, Jörg Beneker, Horst Berzewski, Tareg Bey, Bernd W. Böttiger, Johannes Brockmeier, Christiane J. Bruns, Ute Buerke, Willi Butollo, Jörg Carlsson, Arnd Christoph, Alessandro Cuneo, Albert Diefenbacher, Hans-Georg Dietz, Christian Doehn, Wolf R. Dombrowsky, Wolfgang Eichler, Klaus Ellinger, Detlev Erdmann, Aris Exadaktylos, Matthias Fischer, Helmuth Forst, Klaus Friese, Joachim Gardemann, Harald Genzwürker, Max Geraedts, Günter Germann, Goetz A. Giessler, Frank-Detlef Goebel, Christian Graeb, Jürgen Graf, Nejla Gültekin, Roman L. Haberl, Dirk Härtel, Gerhard Hamann, Margit Heier, Konstantin Heinroth, Ralf Hennen, Harald Herkner, Friedrich Hofmann, Gunter O. Hofmann, Martin Hofmeister, Rüdiger Holzbach, Werner Hosemann, Peter Hügler, Thomas P. H, Karl Peter Ittner, Uwe Janssens, Peter Jehle, Dieter Jocham, Michael Jonas, Franz Kainer, Holger Kaftan, Hans-Peter Kapfhammer, Karl-Georg Kanz, Piotr M. Kasprzak, Holger Kessler, Volker Klauß, Olaf von dem Knesebeck, Carsten König, Thomas Kohler, Martin Kollmann, Reinhard Kopp, Henning Krause, Ulrich van Laak, Christian K. Lackner, Heinz Laubenthal, Tino Laux, Ulrich Lehmann, Hans Lilie, Hartmut Link, Thomas Löscher, Hannelore Löwel, Thomas Luiz, Jörg Martin, Michael Meisel, Christa Meisinger, Frank Merkel, Martin Messelken, Thomas Messer, Wolfgang Meyer, Andreas Mielck, Thomas Mittlmeier, Heinzpeter Moecke, Christian Müller, Marcus Müllner, Wolfgang Mutschler, Michael Nerlich, Thomas Nicolai, Soheyl Noachtar, Christian Ohmann, Maria Overbeck, Randolph Penning, Oliver Peschel, Michael Pfeifer, Bodo Pichler, Stefan Poloczek, Johann Preßl, Roland Prondzinsky, Sebastian Reith, Reinhard Roos, Ansgar Röhrborn, Felix Rosenow, Bernhard. R. Ruf, Matthias Ruppert, Martin Ruß, Fred Salomon, Ulrich Schächinger, Thomas Schlechtriemen, Max Schmauß, Hendrik Schmidt, Thomas K. Schmitt, Joachim Schneider, Peter Sefrin, Clemens Sirtl, Eckhard Sorges, Fabian Spöhr, Tilmann Steinert, Ulrich Tebbe, Andreas Thierbach, Heike Tobien, Gerhard Trabert, Hans-Joachim Trappe, Odo-Winfried Ullrich, Wolfgang Urbach, Peter Vogel, Petra Wacker, Rüdiger Wacker, Frithjof D. Wagner, Marc Warnecke, Tina Wasner, Manfred Weber, Ludwig S. Weilemann, Christoph B. Windisch, Hartmut Winkler, and Heinz Zimmermann

Published
2005
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18. Evidence for Magnetic Field Induced Changes of the Phase of Tunneling States: Spontaneous Echoes in (KBr)$_{1-x}$(KCN)$_x$ in Magnetic Fields

Author

Enss, C. and Ludwig, S.

Subjects
FOS: Physical sciences, Disordered Systems and Neural Networks (cond-mat.dis-nn), Condensed Matter - Disordered Systems and Neural Networks
Abstract

Recently, it has been discovered that in contrast to expectations the low-temperature dielectric properties of some multi-component glasses depend strongly on magnetic fields. In particular, the low-frequency dielectric susceptibility and the amplitude of coherent polarization echoes show striking non-monotonic magnetic field dependencies. The low-temperature dielectric response of these materials is governed by atomic tunneling systems. We now have investigated the coherent properties of tunneling states in a crystalline host in magnetic fields up to 230$ $mT. Two-pulse echo experiments have been performed on a KBr crystal containing about 7.5% CN$^-$. Like in glasses, but perhaps even more surprising in the case of a crystalline system, we observe a very strong magnetic field dependence of the echo amplitude. Moreover, for the first time we have direct evidence that magnetic fields change the phase of coherent tunneling systems in a well-defined way. We present the data and discuss the possible origin of this intriguing effect., Comment: 4 pages, 3 figures, submitted to PRL

Published
2002
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19. Activation of c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) is critical for hypoxia-induced apoptosis of human malignant melanoma

Author

Kunz M, Ibrahim S, Koczan D, Hj, Thiesen, Hj, Köhler, Till Acker, Kh, Plate, Ludwig S, Ur, Rapp, Eb, Bröcker, Gn, Muijen, Flory E, and Gross G

Subjects
Mitogen-Activated Protein Kinase Kinases, Neovascularization, Pathologic, Transcription, Genetic, MAP Kinase Kinase 4, Proto-Oncogene Proteins c-jun, JNK Mitogen-Activated Protein Kinases, Apoptosis, Transfection, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Necrosis, Tumor Cells, Cultured, Humans, Neoplasm Invasiveness, RNA, Messenger, fas Receptor, Mitogen-Activated Protein Kinases, Hypoxia, Melanoma
Abstract

Mitogen-activated protein kinase (MAPK) signaling was examined in malignant melanoma cells exposed to hypoxia. Here we demonstrate that hypoxia induced a strong activation of the c-Jun NH2-terminal kinase (JNK), also termed stress-activated protein kinase (SAPK), in the melanoma cell line 530 in vitro. Other members of the MAPK family, e.g., extracellular signal-regulated kinase and p38, remained unaffected by the hypoxic stimulus. Activated JNK/SAPK could also be observed in the vicinity of hypoxic tumor areas in melanoma metastases as detected by immunohistochemistry. Functional analysis of JNK/SAPK activation in the melanoma cell line 530 revealed that activation of JNK/SAPK is involved in hypoxia-mediated tumor cell apoptosis. Both a dominant negative mutant of JNK/SAPK (SAPKbeta K--R) and a dominant negative mutant of the immediate upstream activator of JNK/SAPK, SEK1 (SEK1 K--R), inhibited hypoxia-induced apoptosis in transient transfection studies. In contrast, overexpression of the wild-type kinases had a slight proapoptotic effect. Inhibition of extracellular signal-regulated kinase and p38 pathways by the chemical inhibitors PD98058 and SB203580, respectively, had no effect on hypoxiainduced apoptosis. Under normoxic conditions, no influence on apoptosis regulation was observed after inhibition of all three MAPK pathways. In contrast to recent findings, JNK/SAPK activation did not correlate with Fas or Fas ligand (FasL) expression, suggesting that the Fas/FasL system is not involved in hypoxia-induced apoptosis in melanoma cells. Taken together, our data demonstrate that hypoxia-induced JNK/SAPK activation appears to play a critical role in apoptosis regulation of melanoma cells in vitro and in vivo, independent of the Fas/FasL system.

Published
2001

20. Activation of c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) is critical for hypoxia-induced apoptosis of human malignant melanoma

Author

Kunz, M., Ibrahim, S., Koczan, D., Thiesen, H.J., Kohler, H.J., Acker, T., Plate, K.H., Ludwig, S., Rapp, U.R., Bröcker, E.B., Muijen, G.N.P. van, Flory, E., and Gross, G.

Subjects
Tumor pathology, Tumor pathologie
Abstract

Item does not contain fulltext Mitogen-activated protein kinase (MAPK) signaling was examined in malignant melanoma cells exposed to hypoxia. Here we demonstrate that hypoxia induced a strong activation of the c-Jun NH2-terminal kinase (JNK), also termed stress-activated protein kinase (SAPK), in the melanoma cell line 530 in vitro. Other members of the MAPK family, e.g., extracellular signal-regulated kinase and p38, remained unaffected by the hypoxic stimulus. Activated JNK/SAPK could also be observed in the vicinity of hypoxic tumor areas in melanoma metastases as detected by immunohistochemistry. Functional analysis of JNK/SAPK activation in the melanoma cell line 530 revealed that activation of JNK/SAPK is involved in hypoxia-mediated tumor cell apoptosis. Both a dominant negative mutant of JNK/SAPK (SAPKbeta K-->R) and a dominant negative mutant of the immediate upstream activator of JNK/SAPK, SEK1 (SEK1 K-->R), inhibited hypoxia-induced apoptosis in transient transfection studies. In contrast, overexpression of the wild-type kinases had a slight proapoptotic effect. Inhibition of extracellular signal-regulated kinase and p38 pathways by the chemical inhibitors PD98058 and SB203580, respectively, had no effect on hypoxiainduced apoptosis. Under normoxic conditions, no influence on apoptosis regulation was observed after inhibition of all three MAPK pathways. In contrast to recent findings, JNK/SAPK activation did not correlate with Fas or Fas ligand (FasL) expression, suggesting that the Fas/FasL system is not involved in hypoxia-induced apoptosis in melanoma cells. Taken together, our data demonstrate that hypoxia-induced JNK/SAPK activation appears to play a critical role in apoptosis regulation of melanoma cells in vitro and in vivo, independent of the Fas/FasL system.

Published
2001

21. Can the S.I.C. Yield Accurate Marketing Data?

Author

Ludwig S. Hellborn

Subjects
Marketing, Computer science, Standard Industrial Classification, Yield (finance), Market analysis, Market data, Heterogeneous information, Business and International Management, Data science, Task (project management), Term (time)
Abstract

IRST of all, the Standard Industrial Classification, being an inanimate and conceptual device, yields nothing by itself. It is the use or application of the S.I.C. in the statistical task of arranging a mass of heterogeneous information into a pattern, intended to be an orderly and meaningful one, that yields breakdowns of statistical data that may or may not be accurate and useful for marketing purposes. Next, let us narrow down what is meant by "marketing data." Most of the basic statistical series dealing with the various aspects of our economy are in a sense marketing data in that they can and are being used for market analysis of various types. The Standard Industrial Classification, however, has found its widest and most useful application in the classification of economic activities inherent in manufacturing. The term "marketing data" is therefore limited to this area.

Published
1956
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24. 3rdinternational workshop on advances in semantic information retrieval

Author

Klyuev, V., Maxim Mozgovoy, Borgo, S., Budzynska, K., Carrara, M., Cybulka, J., Dobrynin, V., Goczyla, K., Haralambous, Y., Homenda, W., Jin, Q., Kaczmarek, J., Kakkonen, T., Kulicki, P., Lai, C., Leonelli, S., Ludwig, S., Martinek, J., Mirenkov, N., Morshed, A., Nalepa, G. J., Palma, R., Piasecki, M., Pyshkin, E., Reformat, M., Shtykh, R., Soldatova, L., Suárez Figueroa Baonza, M. C., Tadeusiewicz, T., Trypuz, R., Vacura, M., Vargiu, E., Vazhenin, A., Wang, H., Wu, S. -H, Zadrozny, S., and Lawrynowicz, A.

25. 3rd international workshop on advances in semantic information retrieval

Author

Klyuev, V., Mozgovoy, M., Borgo, S., Budzynska, K., Carrara, M., Cybulka, J., Dobrynin, V., Goczyla, K., Haralambous, Y., Homenda, W., Jin, Q., Kaczmarek, J., Kakkonen, T., Piotr Kulicki, Lai, C., Leonelli, S., Ludwig, S., Martinek, J., Mirenkov, N., Morshed, A., Nalepa, G. J., Palma, R., Piasecki, M., Pyshkin, E., Reformat, M., Shtykh, R., Soldatova, L., Suárez Figueroa Baonza, M. C., Tadeusiewicz, T., Trypuz, R., Vacura, M., Vargiu, E., Vazhenin, A., Wang, H., Wu, S. -H, Zadrozny, S., and Lawrynowicz, A.

28. NON-INVASIVE MEASUREMENT OF CARDIAC OUTPUT IN ARTIFICIALLY VENTILATED PATIENTS USING THE LUNG PERFUSION CALCULATOR 970

Author

Hans-P. Schuster, Ludwig S. Weilemann, Marion Reu, Jozo Majdandzic, Christoph Rey, and Hans-J. Göldner

Subjects
medicine.medical_specialty, Cardiac output, business.industry, Non invasive, Lung perfusion, Critical Care and Intensive Care Medicine, law.invention, Calculator, law, Anesthesia, Internal medicine, Cardiology, medicine, business
Published
1981
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30. TREATMENT OF ACUTE SEVERE QUINIDINE POISONING. CHARCOAL HEMOPERFUSION OR HEMODIALYSIS?

Author

Jozo Majdandzic, Gilfrich Hj, S. Okonek, Hans-P. Schuster, Ludwig S. Weilemann, and Christoph Rey

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Quinidine poisoning, Critical Care and Intensive Care Medicine, Hemoperfusion, Anesthesia, visual_art, visual_art.visual_art_medium, Medicine, Hemodialysis, business, Intensive care medicine, Charcoal
Published
1981
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32. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

Alison Halliday, Richard Bulbulia, Leo H Bonati, Johanna Chester, Andrea Cradduck-Bamford, Richard Peto, Hongchao Pan, John Potter, Hans Henning Eckstein, Barbara Farrell, Marcus Flather, Averil Mansfield, Boby Mihaylova, Kazim Rahimi, David Simpson, Dafydd Thomas, Peter Sandercock, Richard Gray, Andrew Molyneux, Cliff P Shearman, Peter Rothwell, Anna Belli, Will Herrington, Parminder Judge, Peter Leopold, Marion Mafham, Michael Gough, Piergiorgio Cao, Sumaira MacDonald, Vasha Bari, Clive Berry, S Bradshaw, Wojciech Brudlo, Alison Clarke, Robin Cox, Susan Fathers, Kamran Gaba, Mo Gray, Elizabeth Hayter, Constance Holliday, Rijo Kurien, Michael Lay, Steffi le Conte, Jessica McManus, Zahra Madgwick, Dylan Morris, Andrew Munday, Sandra Pickworth, Wiktor Ostasz, Michiel Poorthuis, Sue Richards, Louisa Teixeira, Sergey Tochlin, Lynda Tully, Carol Wallis, Monique Willet, Alan Young, Renato Casana, Chiara Malloggi, Andrea Odero Jr, Vincenzo Silani, Gianfranco Parati, Giuseppe Malchiodi, Giovanni Malferrari, Francesco Strozzi, Nicola Tusini, Enrico Vecchiati, Gioacchino Coppi, Antonio Lauricella, Roberto Moratto, Roberto Silingardi, Jessica Veronesi, Andrea Zini, Emanuele Ferrero, Michelangelo Ferri, Andrea Gaggiano, Carmelo Labate, Franco Nessi, Daniele Psacharopulo, Andrea Viazzo, Giovanni Malacrida, Daniela Mazzaccaro, Giovanni Meola, Alfredo Modafferi, Giovanni Nano, Maria Teresa Occhiuto, Paolo Righini, Silvia Stegher, Stefano Chiarandini, Filippo Griselli, Sandro Lepidi, Fabio Pozzi Mucelli, Marcello Naccarato, Mario D'Oria, Barbara Ziani, Andrea Stella, Mortalla Dieng, Gianluca Faggioli, Mauro Gargiulo, Sergio Palermo, Rodolfo Pini, Giovanni Maria Puddu, Andrea Vacirca, Domenico Angiletta, Claudio Desantis, Davide Marinazzo, Giovanni Mastrangelo, Guido Regina, Raffaele Pulli, Paolo Bianchi, Lea Cireni, Elisabetta Coppi, Rocco Pizzirusso, Filippo Scalise, Giovanni Sorropago, Valerio Tolva, Valeria Caso, Enrico Cieri, Paola DeRango, Luca Farchioni, Giacomo Isernia, Massimo Lenti, Gian Battista Parlani, Guglielmo Pupo, Grazia Pula, Gioele Simonte, Fabio Verzini, Federico Carimati, Maria Luisa Delodovici, Federico Fontana, Gabriele Piffaretti, Matteo Tozzi, Efrem Civilini, Giorgio Poletto, Bernhard Reimers, Barbara Praquin, Sonia Ronchey, Laura Capoccia, Wassim Mansour, Enrico Sbarigia, Francesco Speziale, Pasqualino Sirignano, Danilo Toni, Roberto Galeotti, Vincenzo Gasbarro, Francesco Mascoli, Tiberio Rocca, Elpiniki Tsolaki, Giulia Bernardini, Ester DeMarco, Alessia Giaquinta, Francesco Patti, Massimiliano Veroux, Pierfrancesco Veroux, Carla Virgilio, Nicola Mangialardi, Matteo Orrico, Vincenzo Di Lazzaro, Nunzio Montelione, Francesco Spinelli, Francesco Stilo, Carlo Cernetti, Sandro Irsara, Giuseppe Maccarrone, Diego Tonello, Adriana Visonà, Beniamino Zalunardo, Emiliano Chisci, Stefano Michelagnoli, Nicola Troisi, Maela Masato, Massimo Dei Negri, Andrea Pacchioni, Salvatore Saccà, Giovanni Amatucci, Alfredo Cannizzaro, Federico Accrocca, Cesare Ambrogi, Renzo Barbazza, Giustino Marcucci, Andrea Siani, Guido Bajardi, Giovanni Savettieri, Angelo Argentieri, Riccardo Corbetta, Attilio Odero, Pietro Quaretti, Federico Z Thyrion, Alessandro Cappelli, Domenico Benevento, Gianmarco De Donato, Maria Agnese Mele, Giancarlo Palasciano, Daniela Pieragalli, Alessandro Rossi, Carlo Setacci, Francesco Setacci, Domenico Palombo, Maria Cecilia Perfumo, Edoardo Martelli, Aldo Paolucci, Santi Trimarchi, Viviana Grassi, Luigi Grimaldi, Giuliana La Rosa, Domenico Mirabella, Matteo Scialabba, Leonildo Sichel, Costantino L D'Angelo, Gian Franco Fadda, Holta Kasemi, Mario Marino, Francesco Burzotta, Francesco Alberto Codispoti, Angela Ferrante, Giovanni Tinelli, Yamume Tshomba, Claudio Vincenzoni, Deborah Amis, Dawn Anderson, Martin Catterson, Mike Clarke, Michelle Davis, Anand Dixit, Alexander Dyker, Gary Ford, Ralph Jackson, Sreevalsan Kappadath, David Lambert, Tim Lees, Stephen Louw, James McCaslin, Noala Parr, Rebecca Robson, Gerard Stansby, Lucy Wales, Vera Wealleans, Lesley Wilson, Michael Wyatt, Hardeep Baht, Ibrahim Balogun, Ilse Burger, Tracy Cosier, Linda Cowie, Gunaratnam Gunathilagan, David Hargroves, Robert Insall, Sally Jones, Hannah Rudenko, Natasha Schumacher, Jawaharlal Senaratne, George Thomas, Audrey Thomson, Tom Webb, Ellen Brown, Bernard Esisi, Ali Mehrzad, Shane MacSweeney, Norman McConachie, Alison Southam, Wayne Sunman, Ahmed Abdul-Hamiq, Jenny Bryce, Ian Chetter, Duncan Ettles, Raghuram Lakshminarayan, Kim Mitchelson, Christopher Rhymes, Graham Robinson, Paul Scott, Alison Vickers, Ray Ashleigh, Stephen Butterfield, Ed Gamble, Jonathan Ghosh, Charles N McCollum, Mark Welch, Sarah Welsh, Leszek Wolowczyk, Mary Donnelly, Stephen D'Souza, Anselm A Egun, Bindu Gregary, Thomas Joseph, Christine Kelly, Shuja Punekar, M Asad Rahi, Sonia Raj, Dare Seriki, George Thomson, James Brown, Ragunath Durairajan, Iris Grunwald, Paul Guyler, Paula Harman, Matthew Jakeways, Christopher Khuoge, Ashish Kundu, Thayalini Loganathan, Nisha Menon, Raji O Prabakaran, Devesh Sinha, Vicky Thompson, Sharon Tysoe, Dennis Briley, Chris Darby, Linda Hands, Dominic Howard, Wilhelm Kuker, Ursula Schulz, Rachel Teal, David Barer, Andrew Brown, Susan Crawford, Paul Dunlop, Ramesh Krishnamurthy, Nikhil Majmudar, Duncan Mitchell, Min P Myint, Richard O'Brien, Janice O'Connell, Naweed Sattar, Shanmugam Vetrivel, Jonathan Beard, Trevor Cleveland, Peter Gaines, John Humphreys, Alison Jenkins, Craig King, Daniel Kusuma, Ralph Lindert, Robbie Lonsdale, Raj Nair, Shah Nawaz, Faith Okhuoya, Douglas Turner, Graham Venables, Paul Dorman, Andrea Hughes, Deborah Jones, David Mendelow, Helen Rodgers, Aidas Raudoniitis, Peter Enevoldson, Hans Nahser, Imelda O'Brien, Francesco Torella, Dave Watling, Richard White, Pauline Brown, Dipankar Dutta, Lorraine Emerson, Paula Hilltout, Sachin Kulkarni, Jackie Morrison, Keith Poskitt, Fiona Slim, Sarah Smith, Amanda Tyler, Joanne Waldron, Mark Whyman, Milda Bajoriene, Lucy Baker, Amanda Colston, Bekky Eliot-Jones, Gita Gramizadeh, Catherine Lewis-Clarke, Laura McCafferty, Deborah Oliver, Debbie Palmer, Abhijeet Patil, Suzannah Pegler, Gopi Ramadurai, Aisling Roberts, Tracey Sargent, Shivaprasad Siddegowda, Ravi Singh-Ranger, Akintunde Williams, Lucy Williams, Steve Windebank, Tadas Zuromskis, Lanka Alwis, Jane Angus, Asaipillai Asokanathan, Caroline Fornolles, Diana Hardy, Sophy Hunte, Frances Justin, Duke Phiri, Marie Mitabouana-Kibou, Lakshmanan Sekaran, Sakthivel Sethuraman, Margaret L Tate, Joyce Akyea-Mensah, Stephen Ball, Angela Chrisopoulou, Elizabeth Keene, Alison Phair, Steven Rogers, John V Smyth, Colin Bicknell, Jeremy Chataway, Nicholas Cheshire, Andrew Clifton, Caroline Eley, Richard Gibbs, Mohammad Hamady, Beth Hazel, Alex James, Michael Jenkins, Nyma Khanom, Austin Lacey, Maz Mireskandari, Joanna O'Reilly, Antony Pereira, Tina Sachs, John Wolfe, Philip Davey, Gill Rogers, Gemma Smith, Gareth Tervit, Ian Nichol, Andrew Parry, Gavin Young, Simon Ashley, James Barwell, Francis Dix, Azlisham M Nor, Chris Parry, Angela Birt, Paul Davies, Jim George, Anne Graham, Leon Jonker, Nicci Kelsall, Caroline Potts, Toni Wilson, Jamie Crinnion, Larissa Cuenoud, Nikola Aleksic, Srdan Babic, Nenad Ilijevski, Đorde Radak, Dragan Sagic, Slobodan Tanaskovic, Momcilo Colic, Vladimir Cvetic, Lazar Davidovic, Dejana R Jovanovic, Igor Koncar, Perica Mutavdžic, Miloš Sladojevic, Ivan Tomic, Eike S Debus, Ulrich Grzyska, Dagmar Otto, Götz Thomalla, Jessica Barlinn, Johannes Gerber, Kathrin Haase, Christian Hartmann, Stefan Ludwig, Volker Pütz, Christian Reeps, Christine Schmidt, Norbert Weiss, Sebastian Werth, Simon Winzer, Janine Gemper, Albrecht Günther, Bianka Heiling, Elisabeth Jochmann, Panagiota Karvouniari, Carsten Klingner, Thomas Mayer, Julia Schubert, Friederike Schulze-Hartung, Jürgen Zanow, Yvonne Bausback, Franka Borger, Spiridon Botsios, Daniela Branzan, Sven Bräunlich, Henryk Hölzer, Janin Lenzer, Christopher Piorkowski, Nadine Richter, Johannes Schuster, Dierk Scheinert, Andrej Schmidt, Holger Staab, Matthias Ulrich, Martin Werner, Hermann Berger, Gábor Biró, Hans-Henning Eckstein, Michael Kallmayer, Kornelia Kreiser, Alexander Zimmermann, Bärbel Berekoven, Klaus Frerker, Vera Gordon, Giovanni Torsello, Sebastian Arnold, Cora Dienel, Martin Storck, Bernhard Biermaier, Hans Martin Gissler, Christof Klötzsch, Tomas Pfeiffer, Ralph Schneider, Leander Söhl, Michael Wennrich, Angelika Alonso, Michael Keese, Christoph Groden, Andreas Cöster, Andreas Engelhardt, Christoph-Maria Ratusinski, Bengt Berg, Martin Delle, Johan Formgren, Peter Gillgren, Lotta Jarl, Torbjörn B Kall, Peter Konrad, Niklas Nyman, Claes Skiöldebrand, Johnny Steuer, Rabbe Takolander, Jonas Malmstedt, Stefan Acosta, Katarina Björses, Kerstin Brandt, Nuno Dias, Anders Gottsäter, Jan Holst, Thorarinn Kristmundsson, Tobias Kühme, Tilo Kölbel, Bengt Lindblad, Mats Lindh, Martin Malina, Tomas Ohrlander, Tim Resch, Viola Rönnle, Björn Sonesson, Margareta Warvsten, Zbigniew Zdanowski, Erik Campbell, Per Kjellin, Hans Lindgren, Johan Nyberg, Björn Petersen, Gunnar Plate, Håkan Pärsson, Peter Qvarfordt, Pavel Ignatenko, Andrey Karpenko, Vladimir Starodubtsev, Mikhail A Chernyavsky, Maria S Golovkova, Boris B Komakha, Nikolay N Zherdev, Andrey Belyasnik, Pavel Chechulov, Dmitry Kandyba, Igor Stepanishchev, Csaba Csobay-Novák, Edit Dósa, László Entz, Balázs Nemes, Zoltán Szeberin, Pál Barzó, Mihaly Bodosi, Eniko Fákó, Béla Fülöp, Tamás Németh, Szilárd Pazdernyik, Krisztina Skoba, Erika Vörös, Eleni Chatzinikou, Athanasios Giannoukas, Christos Karathanos, Stylianos Koutsias, Georgios Kouvelos, Miltiadis Matsagkas, Styliani Ralli, Christos Rountas, Nikolaos Rousas, Konstantinos Spanos, Elias Brountzos, John D Kakisis, Andreas Lazaris, Konstantinos G Moulakakis, Leonidas Stefanis, Georgios Tsivgoulis, Spyros Vasdekis, Constantine N Antonopoulos, Ion Bellenis, Dimitrios Maras, Antonios Polydorou, Victoria Polydorou, Antonios Tavernarakis, Nikolaos Ioannou, Maria Terzoudi, Miltos Lazarides, Michalis Mantatzis, Kostas Vadikolias, Lukasz Dzieciuchowicz, Marcin Gabriel, Zbigniew Krasinski, Grzegorz Oszkinis, Fryderyk Pukacki, Maciej Slowinski, Michal-Goran Stanišic, Ryszard Staniszewski, Jolanta Tomczak, Maciej Zielinski, Piotr Myrcha, Dorota Rózanski, Stanislaw Drelichowski, Wojciech Iwanowski, Katarzyna Koncewicz, Pawel Bialek, Zbigniew Biejat, Wojciech Czepel, Anna Czlonkowska, Anatol Dowzenko, Julia Jedrzejewska, Adam Kobayashi, Jerzy Leszczynski, Andrzej Malek, Jerzy Polanski, Robert Proczka, Maciej Skorski, Mieczyslaw Szostek, Piotr Andziak, Maciej Dratwicki, Robert Gil, Miroslaw Nowicki, Jaroslaw Pniewski, Jaroslaw Rzezak, Piotr Seweryniak, Pawel Dabek, Michal Juszynski, Grzegorz Madycki, Bartosz Pacewski, Witold Raciborski, Piotr Slowinski, Walerian Staszkiewicz, Martin Bombic, Vladimír Chlouba, Jirí Fiedler, Karel Hes, Petr Koštál, Jindrich Sova, Zdenek Kríž, Mojmír Prívara, Michal Reif, Robert Staffa, Robert Vlachovský, Bohuslav Vojtíšek, Tomáš Hrbác, Martin Kuliha, Václav Procházka, Martin Roubec, David Školoudík, David Netuka, Anna Šteklácová, Vladimír Beneš III, Pavel Buchvald, Ladislav Endrych, Miroslav Šercl, Walter Campos Jr, Ivan B Casella, Nelson de Luccia, André E V Estenssoro, Calógero Presti, Pedro Puech-Leão, Celso R B Neves, Erasmo S da Silva, Cid J Sitrângulo Jr, José A T Monteiro, Gisela Tinone, Marcelo Bellini Dalio, Edwaldo E Joviliano, Octávio M Pontes Neto, Mauricio Serra Ribeiro, Patrick Cras, Jeroen M H Hendriks, Mieke Hoppenbrouwers, Patrick Lauwers, Caroline Loos, Laetitia Yperzeele, Mia Geenens, Dimitri Hemelsoet, Isabelle van Herzeele, Frank Vermassen, Parla Astarci, Frank Hammer, Valérie Lacroix, André Peeters, Robert Verhelst, Silvana Cirelli, Pol Dormal, Annelies Grimonprez, Bart Lambrecht, Philipe Lerut, Eddy Thues, Guy De Koster, Quentin Desiron, Alain Maertens de Noordhout, Danielle Malmendier, Mireille Massoz, Georges Saad, Marc Bosiers, Joren Callaert, Koen Deloose, Estrella Blanco Cañibano, Beatriz García Fresnillo, Mercedes Guerra Requena, Pilar C Morata Barrado, Miguel Muela Méndez, Antonio Yusta Izquierdo, Fernando Aparici Robles, Paula Blanes Orti, Luis García Dominguez, Rafael Martínez López, Manuel Miralles Hernández, José I Tembl Ferrairo, Ángel Chamorro, Juan Macho, Víctor Obach, Vincent Riambau, Luis San Román, Frank J Ahlhelm, Kristine Blackham, Stefan Engelter, Thomas Eugster, Henrik Gensicke, Lorenz Gürke, Philippe Lyrer, Luigi Mariani, Marina Maurer, Edin Mujagic, Mandy Müller, Marios Psychogios, Peter Stierli, Christoph Stippich, Christopher Traenka, Thomas Wolff, Benjamin Wagner, Martina M Wiegert, Sandra Clarke, Michael Diepers, Ernst Gröchenig, Philipp Gruber, Andrej Isaak, Timo Kahles, Regula Marti, Krassen Nedeltchev, Luca Remonda, Nadir Tissira, Martina Valença Falcão, Gert J de Borst, Rob H Lo, Frans L Moll, Raechel Toorop, Bart H van der Worp, Evert J Vonken, Jaap L Kappelle, Ommid Jahrome, Floris Vos, Wouter Schuiling, Hendrik van Overhagen, Rudolf W M Keunen, Bob Knippenberg, Jan J Wever, Jan W Lardenoije, Michel Reijnen, Luuk Smeets, Steven van Sterkenburg, Gustav Fraedrich, Elke Gizewski, Ingrid Gruber, Michael Knoflach, Stefan Kiechl, Barbara Rantner, Timur Abdulamit, Patrice Bergeron, Raymond Padovani, Jean-Christophe Trastour, Jean-Marie Cardon, Anne Le Gallou-Wittenberg, Eric Allaire, Jean-Pierre Becquemin, Frédéric Cochennec-Paliwoda, Pascal Desgranges, Hassan Hosseini, Hicham Kobeiter, Jean Marzelle, Mohammed A Almekhlafi, Simerpreet Bal, Phillip A Barber, Shelagh B Coutts, Andrew M Demchuk, Muneer Eesa, Michelle Gillies, Mayank Goyal, Michael D Hill, Mark E Hudon, Anitha Jambula, Carol Kenney, Gary Klein, Marie McClelland, Alim Mitha, Bijoy K Menon, William F Morrish, Steven Peters, Karla J Ryckborst, Greg Samis, Supriya Save, Eric E Smith, Peter Stys, Suresh Subramaniam, Garnette R Sutherland, Tim Watson, John H Wong, L Zimmel, Vojko Flis, Jože Matela, Kazimir Miksic, Franko Milotic, Božidar Mrdja, Barbara Stirn, Erih Tetickovic, Mladen Gasparini, Anton Grad, Ingrid Kompara, Zoren Miloševic, Veronika Palmiste, Toomas Toomsoo, Balzhan Aidashova, Nursultan Kospanov, Roman Lyssenko, Daulet Mussagaliev, Rafi Beyar, Aaron Hoffman, Tony Karram, Arthur Kerner, Eugenia Nikolsky, Samy Nitecki, Silva Andonova, Chavdar Bachvarov, Vesko Petrov, Ivan Cvjetko, Vinko Vidjak, Damir Halužan, Mladen Petrunic, Bao Liu, Chang-Wei Liu, Daniel Bartko, Peter Beno, František Rusnák, Kamil Zelenák, Masayuki Ezura, Takashi Inoue, Naoto Kimura, Ryushi Kondo, Yasushi Matsumoto, Hiroaki Shimizu, Hidenori Endo, Eisuke Furui, Søren Bakke, Kristen Krohg-Sørensen, Terje Nome, Mona Skjelland, Bjørn Tennøe, João Albuquerque e Castro, Gonçalo Alves, Frederico Bastos Gonçalves, José de Aragão Morais, Ana C Garcia, Hugo Valentim, Leonor Vasconcelos, Fernando Belcastro, Fernando Cura, Patricio Zaefferer, Foad Abd-Allah, Mohamed H Eldessoki, Hussein Heshmat Kassem, Haytham Soliman Gharieb, Mary P Colgan, Syed N Haider, Joe Harbison, Prakash Madhavan, Dermot Moore, Gregor Shanik, Viviane Kazan, Munier Nazzal, Vicki Ramsey-Williams, ACST-2 Collaborative Group, Group, ACST-2 Collaborative, Halliday A., Bulbulia R., Bonati L.H., Chester J., Cradduck-Bamford A., Peto R., Pan H., Potter J., Henning Eckstein H., Farrell B., Flather M., Mansfield A., Mihaylova B., Rahimi K., Simpson D., Thomas D., Sandercock P., Gray R., Molyneux A., Shearman C.P., Rothwell P., Belli A., Herrington W., Judge P., Leopold P., Mafham M., Gough M., Cao P., MacDonald S., Bari V., Berry C., Bradshaw S., Brudlo W., Clarke A., Cox R., Fathers S., Gaba K., Gray M., Hayter E., Holliday C., Kurien R., Lay M., le Conte S., McManus J., Madgwick Z., Morris D., Munday A., Pickworth S., Ostasz W., Poorthuis M., Richards S., Teixeira L., Tochlin S., Tully L., Wallis C., Willet M., Young A., Casana R., Malloggi C., Odero A., Silani V., Parati G., Malchiodi G., Malferrari G., Strozzi F., Tusini N., Vecchiati E., Coppi G., Lauricella A., Moratto R., Silingardi R., Veronesi J., Zini A., Ferrero E., Ferri M., Gaggiano A., Labate C., Nessi F., Psacharopulo D., Viazzo A., Malacrida G., Mazzaccaro D., Meola G., Modafferi A., Nano G., Occhiuto M.T., Righini P., Stegher S., Chiarandini S., Griselli F., Lepidi S., Pozzi Mucelli F., Naccarato M., D'Oria M., Ziani B., Stella A., Dieng M., Faggioli G., Gargiulo M., Palermo S., Pini R., Puddu G.M., Vacirca A., Angiletta D., Desantis C., Marinazzo D., Mastrangelo G., Regina G., Pulli R., Bianchi P., Cireni L., Coppi E., Pizzirusso R., Scalise F., Sorropago G., Tolva V., Caso V., Cieri E., DeRango P., Farchioni L., Isernia G., Lenti M., Parlani G.B., Pupo G., Pula G., Simonte G., Verzini F., Carimati F., Delodovici M.L., Fontana F., Piffaretti G., Tozzi M., Civilini E., Poletto G., Reimers B., Praquin B., Ronchey S., Capoccia L., Mansour W., Sbarigia E., Speziale F., Sirignano P., Toni D., Galeotti R., Gasbarro V., Mascoli F., Rocca T., Tsolaki E., Bernardini G., DeMarco E., Giaquinta A., Patti F., Veroux M., Veroux P., Virgilio C., Mangialardi N., Orrico M., Di Lazzaro V., Montelione N., Spinelli F., Stilo F., Cernetti C., Irsara S., Maccarrone G., Tonello D., Visona A., Zalunardo B., Chisci E., Michelagnoli S., Troisi N., Masato M., Dei Negri M., Pacchioni A., Sacca S., Amatucci G., Cannizzaro A., Accrocca F., Ambrogi C., Barbazza R., Marcucci G., Siani A., Bajardi G., Savettieri G., Argentieri A., Corbetta R., Quaretti P., Thyrion F.Z., Cappelli A., Benevento D., De Donato G., Mele M.A., Palasciano G., Pieragalli D., Rossi A., Setacci C., Setacci F., Palombo D., Perfumo M.C., Martelli E., Paolucci A., Trimarchi S., Grassi V., Grimaldi L., La Rosa G., Mirabella D., Scialabba M., Sichel L., D'Angelo C.L., Fadda G.F., Kasemi H., Marino M., Burzotta F., Codispoti F.A., Ferrante A., Tinelli G., Tshomba Y., Vincenzoni C., Amis D., Anderson D., Catterson M., Clarke M., Davis M., Dixit A., Dyker A., Ford G., Jackson R., Kappadath S., Lambert D., Lees T., Louw S., McCaslin J., Parr N., Robson R., Stansby G., Wales L., Wealleans V., Wilson L., Wyatt M., Baht H., Balogun I., Burger I., Cosier T., Cowie L., Gunathilagan G., Hargroves D., Insall R., Jones S., Rudenko H., Schumacher N., Senaratne J., Thomas G., Thomson A., Webb T., Brown E., Esisi B., Mehrzad A., MacSweeney S., McConachie N., Southam A., Sunman W., Abdul-Hamiq A., Bryce J., Chetter I., Ettles D., Lakshminarayan R., Mitchelson K., Rhymes C., Robinson G., Scott P., Vickers A., Ashleigh R., Butterfield S., Gamble E., Ghosh J., McCollum C.N., Welch M., Welsh S., Wolowczyk L., Donnelly M., D'Souza S., Egun A.A., Gregary B., Joseph T., Kelly C., Punekar S., Rahi M.A., Raj S., Seriki D., Thomson G., Brown J., Durairajan R., Grunwald I., Guyler P., Harman P., Jakeways M., Khuoge C., Kundu A., Loganathan T., Menon N., Prabakaran R.O., Sinha D., Thompson V., Tysoe S., Briley D., Darby C., Hands L., Howard D., Kuker W., Schulz U., Teal R., Barer D., Brown A., Crawford S., Dunlop P., Krishnamurthy R., Majmudar N., Mitchell D., Myint M.P., O'Brien R., O'Connell J., Sattar N., Vetrivel S., Beard J., Cleveland T., Gaines P., Humphreys J., Jenkins A., King C., Kusuma D., Lindert R., Lonsdale R., Nair R., Nawaz S., Okhuoya F., Turner D., Venables G., Dorman P., Hughes A., Jones D., Mendelow D., Rodgers H., Raudoniitis A., Enevoldson P., Nahser H., O'Brien I., Torella F., Watling D., White R., Brown P., Dutta D., Emerson L., Hilltout P., Kulkarni S., Morrison J., Poskitt K., Slim F., Smith S., Tyler A., Waldron J., Whyman M., Bajoriene M., Baker L., Colston A., Eliot-Jones B., Gramizadeh G., Lewis-Clarke C., McCafferty L., Oliver D., Palmer D., Patil A., Pegler S., Ramadurai G., Roberts A., Sargent T., Siddegowda S., Singh-Ranger R., Williams A., Williams L., Windebank S., Zuromskis T., Alwis L., Angus J., Asokanathan A., Fornolles C., Hardy D., Hunte S., Justin F., Phiri D., Mitabouana-Kibou M., Sekaran L., Sethuraman S., Tate M.L., Akyea-Mensah J., Ball S., Chrisopoulou A., Keene E., Phair A., Rogers S., Smyth J.V., Bicknell C., Chataway J., Cheshire N., Clifton A., Eley C., Gibbs R., Hamady M., Hazel B., James A., Jenkins M., Khanom N., Lacey A., Mireskandari M., O'Reilly J., Pereira A., Sachs T., Wolfe J., Davey P., Rogers G., Smith G., Tervit G., Nichol I., Parry A., Young G., Ashley S., Barwell J., Dix F., Nor A.M., Parry C., Birt A., Davies P., George J., Graham A., Jonker L., Kelsall N., Potts C., Wilson T., Crinnion J., Cuenoud L., Aleksic N., Babic S., Ilijevski N., Radak, Sagic D., Tanaskovic S., Colic M., Cvetic V., Davidovic L., Jovanovic D.R., Koncar I., Mutavdzic P., Sladojevic M., Tomic I., Debus E.S., Grzyska U., Otto D., Thomalla G., Barlinn J., Gerber J., Haase K., Hartmann C., Ludwig S., Putz V., Reeps C., Schmidt C., Weiss N., Werth S., Winzer S., Gemper J., Gunther A., Heiling B., Jochmann E., Karvouniari P., Klingner C., Mayer T., Schubert J., Schulze-Hartung F., Zanow J., Bausback Y., Borger F., Botsios 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Subjects
Male, medicine.medical_specialty, Time Factors, Time Factor, medicine.medical_treatment, Carotid Stenosi, MEDLINE, Carotid endarterectomy, Rate ratio, Risk Assessment, Asymptomatic, law.invention, Randomized controlled trial, law, Risk Factors, carotid artery stenting (CAS), carotid endarterectomy (CEA), Stent, medicine, Humans, Carotid Stenosis, Stroke, Endarterectomy, Aged, Endarterectomy, Carotid, business.industry, carotid artery, Risk Factor, Articles, General Medicine, trial, medicine.disease, Settore MED/22 - CHIRURGIA VASCOLARE, Surgery, Stenosis, Treatment Outcome, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Female, Stents, Human medicine, medicine.symptom, business, Human
Abstract

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Published
2021

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