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4. Characterization of antimicrobial use and co-infections among hospitalized patients with COVID-19: a prospective observational cohort study

Author

Lingscheid, Tilman, Lippert, Lena J., Hillus, David, Kruis, Tassilo, Thibeault, Charlotte, Helbig, Elisa T., Tober-Lau, Pinkus, Pfäfflin, Frieder, Müller-Redetzky, Holger, Witzenrath, Martin, Zoller, Thomas, Uhrig, Alexander, Opitz, Bastian, Suttorp, Norbert, Kramer, Tobias S., Sander, Leif E., Stegemann, Miriam S., and Kurth, Florian

Published
2022
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5. Functional limitations 12 months after SARS-CoV-2 infection correlate with initial disease severity: An observational study of cardiopulmonary exercise capacity testing in COVID-19 convalescents

Author

Steinbeis, Fridolin, Knape, Philipp, Mittermaier, Mirja, Helbig, Elisa Theresa, Tober-Lau, Pinkus, Thibeault, Charlotte, Lippert, Lena Johanna, Xiang, Weiwei, Müller-Plathe, Moritz, Steinbrecher, Sarah, Meyer, Hans-Jakob, Ring, Raphaela Maria, Ruwwe-Glösenkamp, Christoph, Alius, Florian, Li, Yaosi, Müller-Redetzky, Holger, Uhrig, Alexander, Lingscheid, Tilman, Grund, Daniel, Temmesfeld-Wollbrück, Bettina, Suttorp, Norbert, Sander, Leif Erik, Kurth, Florian, Witzenrath, Martin, and Zoller, Thomas

Published
2022
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6. A time-resolved proteomic and prognostic map of COVID-19

Author

Kleinschmidt, Malte, Heim, Katrin M., Millet, Belén, Meyer-Arndt, Lil, Hübner, Ralf H., Andermann, Tim, Doehn, Jan M., Opitz, Bastian, Sawitzki, Birgit, Grund, Daniel, Radünzel, Peter, Schürmann, Mariana, Zoller, Thomas, Alius, Florian, Knape, Philipp, Breitbart, Astrid, Li, Yaosi, Bremer, Felix, Pergantis, Panagiotis, Schürmann, Dirk, Temmesfeld-Wollbrück, Bettina, Wendisch, Daniel, Brumhard, Sophia, Haenel, Sascha S., Conrad, Claudia, Georg, Philipp, Eckardt, Kai-Uwe, Lehner, Lukas, Kruse, Jan M., Ferse, Carolin, Körner, Roland, Spies, Claudia, Edel, Andreas, Weber-Carstens, Steffen, Krannich, Alexander, Zvorc, Saskia, Li, Linna, Behrens, Uwe, Schmidt, Sein, Rönnefarth, Maria, Dang-Heine, Chantip, Röhle, Robert, Lieker, Emma, Kretzler, Lucie, Wirsching, Isabelle, Wollboldt, Christian, Wu, Yinan, Schwanitz, Georg, Hillus, David, Kasper, Stefanie, Olk, Nadine, Horn, Alexandra, Briesemeister, Dana, Treue, Denise, Hummel, Michael, Corman, Victor M., Drosten, Christian, von Kalle, Christof, Demichev, Vadim, Tober-Lau, Pinkus, Lemke, Oliver, Nazarenko, Tatiana, Thibeault, Charlotte, Whitwell, Harry, Röhl, Annika, Freiwald, Anja, Szyrwiel, Lukasz, Ludwig, Daniela, Correia-Melo, Clara, Aulakh, Simran Kaur, Helbig, Elisa T., Stubbemann, Paula, Lippert, Lena J., Grüning, Nana-Maria, Blyuss, Oleg, Vernardis, Spyros, White, Matthew, Messner, Christoph B., Joannidis, Michael, Sonnweber, Thomas, Klein, Sebastian J., Pizzini, Alex, Wohlfarter, Yvonne, Sahanic, Sabina, Hilbe, Richard, Schaefer, Benedikt, Wagner, Sonja, Mittermaier, Mirja, Machleidt, Felix, Garcia, Carmen, Ruwwe-Glösenkamp, Christoph, Lingscheid, Tilman, Bosquillon de Jarcy, Laure, Stegemann, Miriam S., Pfeiffer, Moritz, Jürgens, Linda, Denker, Sophy, Zickler, Daniel, Enghard, Philipp, Zelezniak, Aleksej, Campbell, Archie, Hayward, Caroline, Porteous, David J., Marioni, Riccardo E., Uhrig, Alexander, Müller-Redetzky, Holger, Zoller, Heinz, Löffler-Ragg, Judith, Keller, Markus A., Tancevski, Ivan, Timms, John F., Zaikin, Alexey, Hippenstiel, Stefan, Ramharter, Michael, Witzenrath, Martin, Suttorp, Norbert, Lilley, Kathryn, Mülleder, Michael, Sander, Leif Erik, Ralser, Markus, and Kurth, Florian

Published
2021
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7. Short- and long-term T cell and antibody responses following dexamethasone treatment in COVID-19

Author

Thibeault, Charlotte, primary, Bardtke, Lara, additional, Vanshylla, Kanika, additional, di Cristanziano, Veronica, additional, Eberhardt, Kirsten A., additional, Stubbemann, Paula, additional, Hillus, David, additional, Tober-Lau, Pinkus, additional, Mukherjee, Parnika, additional, Münn, Friederike, additional, Lippert, Lena J., additional, Helbig, Elisa T., additional, Lingscheid, Tilman, additional, Steinbeis, Fridolin, additional, Mittermaier, Mirja, additional, Witzenrath, Martin, additional, Zoller, Thomas, additional, Klein, Florian, additional, Sander, Leif E., additional, and Kurth, Florian, additional

Published
2023
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8. Post-treatment haemolysis is common following oral artemisinin combination therapy of uncomplicated malaria in travellers

Author

Kurth, Florian, primary, Tober-Lau, Pinkus, additional, Lingscheid, Tilman, additional, Bardtke, Lara, additional, Kim, Johanna, additional, Angheben, Andrea, additional, Gobbi, Federico G, additional, Mbavu, Lena, additional, Stegemann, Miriam S, additional, Heim, Katrin M, additional, Pfäfflin, Frieder, additional, Menner, Nikolai, additional, Schürmann, Mariana, additional, Mikolajewska, Agata, additional, Witzenrath, Martin, additional, Sander, Leif E, additional, Mayer, Beate, additional, and Zoller, Thomas, additional

Published
2023
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9. Pharmacokinetics of Nirmatrelvir and Ritonavir in COVID-19 Patients with End-Stage Renal Disease on Intermittent Hemodialysis

Author

Lingscheid, Tilman, primary, Kinzig, Martina, additional, Krüger, Anne, additional, Müller, Nils, additional, Bölke, Georg, additional, Tober-Lau, Pinkus, additional, Münn, Friederike, additional, Kriedemann, Helene, additional, Witzenrath, Martin, additional, Sander, Leif E., additional, Sörgel, Fritz, additional, and Kurth, Florian, additional

Published
2022
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10. A proteomic survival predictor for COVID-19 patients in intensive care

Author

Demichev, Vadim, Tober-Lau, Pinkus, Nazarenko, Tatiana, Lemke, Oliver, Kaur Aulakh, Simran, Whitwell, Harry J, Röhl, Annika, Freiwald, Anja, Mittermaier, Mirja, Szyrwiel, Lukasz, Ludwig, Daniela, Correia-Melo, Clara, Lippert, Lena J, Helbig, Elisa T, Stubbemann, Paula, Olk, Nadine, Thibeault, Charlotte, Grüning, Nana-Maria, Blyuss, Oleg, Vernardis, Spyros, White, Matthew, Messner, Christoph B, Joannidis, Michael, Sonnweber, Thomas, Klein, Sebastian J, Pizzini, Alex, Wohlfarter, Yvonne, Sahanic, Sabina, Hilbe, Richard, Schaefer, Benedikt, Wagner, Sonja, Machleidt, Felix, Garcia, Carmen, Ruwwe-Glösenkamp, Christoph, Lingscheid, Tilman, Bosquillon De Jarcy, Laure, Stegemann, Miriam S, Pfeiffer, Moritz, Jürgens, Linda, Denker, Sophy, Zickler, Daniel, Spies, Claudia, Edel, Andreas, Müller, Nils B, Enghard, Philipp, Zelezniak, Aleksej, Bellmann-Weiler, Rosa, Weiss, Günter, Campbell, Archie, Hayward, Caroline, Porteous, David J, Marioni, Riccardo E, Uhrig, Alexander, Zoller, Heinz, Löffler-Ragg, Judith, Keller, Markus A, Tancevski, Ivan, Timms, John F, Zaikin, Alexey, Hippenstiel, Stefan, Ramharter, Michael, Müller-Redetzky, Holger, Witzenrath, Martin, Suttorp, Norbert, Lilley, Kathryn, Mülleder, Michael, Sander, Leif Erik, PA-COVID-19 Study Group, Kurth, Florian, Ralser, Markus, Demichev, Vadim [0000-0002-2424-9412], Nazarenko, Tatiana [0000-0002-4245-7346], Kaur Aulakh, Simran [0000-0002-1580-7144], Whitwell, Harry J [0000-0001-8987-4158], Röhl, Annika [0000-0003-3924-6422], Mittermaier, Mirja [0000-0003-0678-6676], Szyrwiel, Lukasz [0000-0003-1983-2950], Correia-Melo, Clara [0000-0001-6062-1472], Lippert, Lena J [0000-0002-8337-1311], Helbig, Elisa T [0000-0003-4276-7974], Thibeault, Charlotte [0000-0002-8979-9386], Grüning, Nana-Maria [0000-0002-1528-6625], Blyuss, Oleg [0000-0002-0194-6389], Vernardis, Spyros [0000-0002-3946-1686], White, Matthew [0000-0003-0923-974X], Pizzini, Alex [0000-0003-3699-1822], Wohlfarter, Yvonne [0000-0002-0988-9411], Hilbe, Richard [0000-0001-9987-109X], Schaefer, Benedikt [0000-0001-8690-2774], Wagner, Sonja [0000-0003-2319-2722], Machleidt, Felix [0000-0002-6108-5269], Garcia, Carmen [0000-0002-6859-1084], Ruwwe-Glösenkamp, Christoph [0000-0001-5077-829X], Lingscheid, Tilman [0000-0001-5377-3152], Stegemann, Miriam S [0000-0002-7968-0429], Denker, Sophy [0000-0002-0736-6019], Edel, Andreas [0000-0002-9951-7223], Müller, Nils B [0000-0001-8918-857X], Zelezniak, Aleksej [0000-0002-3098-9441], Bellmann-Weiler, Rosa [0000-0002-5584-111X], Campbell, Archie [0000-0003-0198-5078], Hayward, Caroline [0000-0002-9405-9550], Porteous, David J [0000-0003-1249-6106], Uhrig, Alexander [0000-0001-7474-6743], Zoller, Heinz [0000-0003-1794-422X], Keller, Markus A [0000-0002-8654-9920], Tancevski, Ivan [0000-0001-5116-8960], Zaikin, Alexey [0000-0001-7540-1130], Ramharter, Michael [0000-0002-9259-1885], Witzenrath, Martin [0000-0002-9787-5633], Mülleder, Michael [0000-0001-9792-3861], Sander, Leif Erik [0000-0002-0476-9947], Kurth, Florian [0000-0002-3807-473X], and Apollo - University of Cambridge Repository

Subjects
Chemical Biology & High Throughput, PA-COVID-19 Study group, Metabolism, Ecology,Evolution & Ethology, Synthetic Biology, Computational & Systems Biology
Abstract

Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.

Published
2022
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11. Initial Experience With SARS-CoV-2-Neutralizing Monoclonal Antibodies in Kidney or Combined Kidney-Pancreas Transplant Recipients

Author

Bachmann, Friederike, primary, Budde, Klemens, additional, Suttorp, Norbert, additional, Lingscheid, Tilman, additional, Stegemann, Miriam Songa, additional, Osmanodja, Bilgin, additional, Schrezenmeier, Eva, additional, Duettmann, Wiebke, additional, Weber, Ulrike, additional, Naik, Marcel, additional, Lehner, Lukas Johannes, additional, Kahl, Andreas, additional, Duerr, Michael, additional, Eckardt, Kai-Uwe, additional, Waiser, Johannes, additional, Choi, Mira, additional, and Halleck, Fabian, additional

Published
2022
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12. A time-resolved proteomic and prognostic map of COVID-19

Author

Demichev, Vadim, Tober-Lau, Pinkus, Lemke, Oliver, Nazarenko, Tatiana, Thibeault, Charlotte, Whitwell, Harry, Röhl, Annika, Freiwald, Anja, Szyrwiel, Lukasz, Ludwig, Daniela, Correia-Melo, Clara, Aulakh, Simran Kaur, Helbig, Elisa T, Stubbemann, Paula, Lippert, Lena J, Grüning, Nana-Maria, Blyuss, Oleg, Vernardis, Spyros, White, Matthew, Messner, Christoph B, Joannidis, Michael, Sonnweber, Thomas, Klein, Sebastian J, Pizzini, Alex, Wohlfarter, Yvonne, Sahanic, Sabina, Hilbe, Richard, Schaefer, Benedikt, Wagner, Sonja, Mittermaier, Mirja, Machleidt, Felix, Garcia, Carmen, Ruwwe-Glösenkamp, Christoph, Lingscheid, Tilman, Bosquillon De Jarcy, Laure, Stegemann, Miriam S, Pfeiffer, Moritz, Jürgens, Linda, Denker, Sophy, Zickler, Daniel, Enghard, Philipp, Zelezniak, Aleksej, Campbell, Archie, Hayward, Caroline, Porteous, David J, Marioni, Riccardo E, Uhrig, Alexander, Müller-Redetzky, Holger, Zoller, Heinz, Löffler-Ragg, Judith, Keller, Markus A, Tancevski, Ivan, Timms, John F, Zaikin, Alexey, Hippenstiel, Stefan, Ramharter, Michael, Witzenrath, Martin, Suttorp, Norbert, Lilley, Kathryn, Mülleder, Michael, Sander, Leif Erik, PA-COVID-19 Study Group, Ralser, Markus, Kurth, Florian, Lilley, Kathryn [0000-0003-0594-6543], and Apollo - University of Cambridge Repository

Subjects
Chemical Biology & High Throughput, Inflammation, Proteomics, Proteome, clinical disease progression, SARS-CoV-2, Age Factors, COVID-19, biomarkers, Prognosis, disease prognosis, Blood Cell Count, Enzyme Activation, Machine Learning, Metabolism, Ecology,Evolution & Ethology, physiological parameters, Disease Progression, Humans, Synthetic Biology, Blood Gas Analysis, longitudinal profiling, patient trajectories, Computational & Systems Biology
Abstract

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.

Published
2021

13. Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Author

Thibeault, Charlotte, Mühlemann, Barbara, Helbig, Elisa T, Mittermaier, Mirja, Lingscheid, Tilman, Tober-Lau, Pinkus, Meyer-Arndt, Lil A, Meiners, Leonie, Stubbemann, Paula, Haenel, Sascha S, Bosquillon De Jarcy, Laure, Lippert, Lena, Pfeiffer, Moritz, Stegemann, Miriam S, Roehle, Robert, Wiebach, Janine, Hippenstiel, Stefan, Zoller, Thomas, Müller-Redetzky, Holger, Uhrig, Alexander, Balzer, Felix, Von Kalle, Christof, Suttorp, Norbert, Jones, Terry C, Drosten, Christian, Witzenrath, Martin, Sander, Leif E, Pa-COVID Study Group, Corman, Victor M, Kurth, Florian, Kurth, Florian [0000-0002-3807-473X], and Apollo - University of Cambridge Repository

Subjects
Time Factors, COVID-19 nucleic acid testing, Respiratory distress syndrome, Viral concentration, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Symptom assessment, COVID-19, Viral Load, Respiration, Artificial, Virus Shedding, Coronavirus disease 2019 (COVID-19), Cohort Studies, Hospitalization, Tertiary Care Centers, Kinetics, Artificial respiration, Mechanical ventilation, Risk Factors, Germany, Hypertension, Humans, Prospective Studies, Prospective study
Abstract

Funder: Humboldt-Universität zu Berlin (1034), PURPOSE: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. METHODS: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. RESULTS: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. CONCLUSIONS: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19.

Published
2021

14. Impact of dexamethasone on SARS-CoV-2 concentration kinetics and antibody response in hospitalized COVID-19 patients: results from a prospective observational study

Author

Mühlemann, Barbara, primary, Thibeault, Charlotte, additional, Hillus, David, additional, Helbig, Elisa T., additional, Lippert, Lena J., additional, Tober-Lau, Pinkus, additional, Schwarz, Tatjana, additional, Müller, Marcel A., additional, Witzenrath, Martin, additional, Suttorp, Norbert, additional, Sander, Leif E., additional, Drosten, Christian, additional, Jones, Terry C., additional, Corman, Victor M., additional, Kurth, Florian, additional, Hippenstiel, Stefan, additional, Haenel, Sascha S., additional, Mittermaier, Mirja, additional, Steinbeis, Fridolin, additional, Lingscheid, Tilman, additional, Temmesfeld-Wollbrück, Bettina, additional, Zoller, Thomas, additional, Müller-Redetzky, Holger, additional, Uhrig, Alexander, additional, Grund, Daniel, additional, Ruwwe-Glösenkamp, Christoph, additional, Stegemann, Miriam S., additional, Heim, Katrin M., additional, Hübner, Ralf H., additional, Opitz, Bastian, additional, Eckardt, Kai-Uwe, additional, Möckel, Martin, additional, Balzer, Felix, additional, Spies, Claudia, additional, Weber-Carstens, Steffen, additional, Tacke, Frank, additional, Dang-Heine, Chantip, additional, Hummel, Michael, additional, Schwanitz, Georg, additional, Behrens, Uwe D., additional, Rönnefarth, Maria, additional, Schmidt, Sein, additional, Krannich, Alexander, additional, von Kalle, Christof, additional, Jürgens, Linda, additional, Kleinschmidt, Malte, additional, Denker, Sophy, additional, Pfeiffer, Moritz, additional, Pascual-Leone, Belén Millet, additional, Mrziglod, Luisa, additional, Machleidt, Felix, additional, Albus, Sebastian, additional, Bremer, Felix, additional, Doehn, Jan-Moritz, additional, Andermann, Tim, additional, Garcia, Carmen, additional, Knape, Philipp, additional, Krause, Philipp M., additional, Lechtenberg, Liron, additional, Li, Yaosi, additional, Pergantis, Panagiotis, additional, Jacobi, Till, additional, Ritter, Teresa, additional, Yedikat, Berna, additional, Pfannkuch, Lennart, additional, Zobel, Christian, additional, Kellermann, Ute, additional, Fieberg, Susanne, additional, Bosquillon de Jarcy, Laure, additional, Wetzel, Anne, additional, Tabeling, Christoph, additional, Brack, Markus C., additional, Müller-Plathe, Moritz, additional, Kruse, Jan M., additional, Zickler, Daniel, additional, Edel, Andreas, additional, Stier, Britta, additional, Körner, Roland, additional, Müller, Nils B., additional, Enghard, Philipp, additional, Stubbemann, Paula, additional, Olk, Nadine, additional, Koch, Willi M., additional, Horn, Alexandra, additional, Stoyanova, Katrin K., additional, Zvorc, Saskia, additional, Kretzler, Lucie, additional, Meyer-Arndt, Lil A., additional, Li, Linna, additional, Wirsching, Isabelle, additional, Treue, Denise, additional, Briesemeister, Dana, additional, Schlesinger, Jenny, additional, Sawitzki, Birgit, additional, Bardtke, Lara, additional, Pohl, Kai, additional, Georg, Philipp, additional, Wendisch, Daniel, additional, Hiller, Anna L., additional, Brumhard, Sophie, additional, Schmidt, Marie Luisa, additional, Meiners, Leonie, additional, and Tscheak, Patricia, additional

Published
2021
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15. A time-resolved proteomic and prognostic map of COVID-19

Author

Demichev, Vadim, primary, Tober-Lau, Pinkus, additional, Lemke, Oliver, additional, Nazarenko, Tatiana, additional, Thibeault, Charlotte, additional, Whitwell, Harry, additional, Röhl, Annika, additional, Freiwald, Anja, additional, Szyrwiel, Lukasz, additional, Ludwig, Daniela, additional, Correia-Melo, Clara, additional, Aulakh, Simran Kaur, additional, Helbig, Elisa T., additional, Stubbemann, Paula, additional, Lippert, Lena J., additional, Grüning, Nana-Maria, additional, Blyuss, Oleg, additional, Vernardis, Spyros, additional, White, Matthew, additional, Messner, Christoph B., additional, Joannidis, Michael, additional, Sonnweber, Thomas, additional, Klein, Sebastian J., additional, Pizzini, Alex, additional, Wohlfarter, Yvonne, additional, Sahanic, Sabina, additional, Hilbe, Richard, additional, Schaefer, Benedikt, additional, Wagner, Sonja, additional, Mittermaier, Mirja, additional, Machleidt, Felix, additional, Garcia, Carmen, additional, Ruwwe-Glösenkamp, Christoph, additional, Lingscheid, Tilman, additional, Bosquillon de Jarcy, Laure, additional, Stegemann, Miriam S., additional, Pfeiffer, Moritz, additional, Jürgens, Linda, additional, Denker, Sophy, additional, Zickler, Daniel, additional, Enghard, Philipp, additional, Zelezniak, Aleksej, additional, Campbell, Archie, additional, Hayward, Caroline, additional, Porteous, David J., additional, Marioni, Riccardo E., additional, Uhrig, Alexander, additional, Müller-Redetzky, Holger, additional, Zoller, Heinz, additional, Löffler-Ragg, Judith, additional, Keller, Markus A., additional, Tancevski, Ivan, additional, Timms, John F., additional, Zaikin, Alexey, additional, Hippenstiel, Stefan, additional, Ramharter, Michael, additional, Witzenrath, Martin, additional, Suttorp, Norbert, additional, Lilley, Kathryn, additional, Mülleder, Michael, additional, Sander, Leif Erik, additional, Ralser, Markus, additional, Kurth, Florian, additional, Kleinschmidt, Malte, additional, Heim, Katrin M., additional, Millet, Belén, additional, Meyer-Arndt, Lil, additional, Hübner, Ralf H., additional, Andermann, Tim, additional, Doehn, Jan M., additional, Opitz, Bastian, additional, Sawitzki, Birgit, additional, Grund, Daniel, additional, Radünzel, Peter, additional, Schürmann, Mariana, additional, Zoller, Thomas, additional, Alius, Florian, additional, Knape, Philipp, additional, Breitbart, Astrid, additional, Li, Yaosi, additional, Bremer, Felix, additional, Pergantis, Panagiotis, additional, Schürmann, Dirk, additional, Temmesfeld-Wollbrück, Bettina, additional, Wendisch, Daniel, additional, Brumhard, Sophia, additional, Haenel, Sascha S., additional, Conrad, Claudia, additional, Georg, Philipp, additional, Eckardt, Kai-Uwe, additional, Lehner, Lukas, additional, Kruse, Jan M., additional, Ferse, Carolin, additional, Körner, Roland, additional, Spies, Claudia, additional, Edel, Andreas, additional, Weber-Carstens, Steffen, additional, Krannich, Alexander, additional, Zvorc, Saskia, additional, Li, Linna, additional, Behrens, Uwe, additional, Schmidt, Sein, additional, Rönnefarth, Maria, additional, Dang-Heine, Chantip, additional, Röhle, Robert, additional, Lieker, Emma, additional, Kretzler, Lucie, additional, Wirsching, Isabelle, additional, Wollboldt, Christian, additional, Wu, Yinan, additional, Schwanitz, Georg, additional, Hillus, David, additional, Kasper, Stefanie, additional, Olk, Nadine, additional, Horn, Alexandra, additional, Briesemeister, Dana, additional, Treue, Denise, additional, Hummel, Michael, additional, Corman, Victor M., additional, Drosten, Christian, additional, and von Kalle, Christof, additional

Published
2021
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18. Outpatient treatment of imported uncomplicated Plasmodium falciparum malaria: results from a survey among TropNet and GeoSentinel experts for tropical medicine

Author

Lingscheid, Tilman, primary, Kurth, Florian, primary, Stegemann, Miriam S, primary, Clerinx, Jan, primary, Calleri, Guido, primary, Rothe, Camilla, primary, Angheben, Andrea, primary, Gobbi, Federico, primary, Bisoffi, Zeno, primary, Hamer, Davidson H, primary, Libman, Michael, primary, Hatz, Christoph, primary, and Zoller, Thomas, primary

Published
2020
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19. Schistosomiasis in European travelers and migrants

Author

Lingscheid, Tilman

Subjects
bilharzia, schistosomiasis, snail fever, travel medicine, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, tropical disease
Abstract

Introduction: Schistosomiasis is a parasitic disease of high prevalence; it is a major global public health concern with more than 200 million people affected in 78 tropical to subtropical countries. However, in schistosomiasis non-endemic countries the infection is also regularly found among returning travellers and migrants from endemic countries. Methods: The European Network for Tropical Medicine and Travel Health conducted a surveillance study on imported schistosomiasis to Europe between the years 1997 and 2010. Clinical and demographic data of returning travelers or migrants were collected. The objective of the study was to provide clinical and epidemiological data on imported schistosomiasis in Europe. In addition we aimed for specification of geographical information. Another goal was the identification of risk factors associated with infection among travelers or migrants. Results: Overall 1,465 cases of imported schistosomiasis to Europe were analyzed. 486 (33%) cases were found among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-Europeans. 18.6% of patients had received pretravel advice; migrants already living in Europe, traveling to visit friends and relatives (VFRs) made negligible use of pretravel advice. Nearly all infections (95%) were acquired on the African continent. Travelers acquired schistosomiasis mostly in Eastern Africa and certain countries in Western Africa, whereas migrants showed a scattered epidemiology on the African continent with predominance in Western Africa. Schistosoma mansoni was found in 570 patients (39%) and Schistosoma haematobium in 318 patients (22%). Overall, 57.5% of patients were symptomatic; 27% of patients presented with acute symptoms. Patients with acute symptoms reported earlier within 3 months to a TropNet center after returning. Microscopy and serology were the most commonly used diagnostic tools – among symptomatic and asymptomatic patients. Conclusion: Schistosomiasis is a relevant travel-related / imported infection among travelers and migrants to Europe. Use of pretravel advice was low among all travelers, especially among VFR travelers. Therefore, efforts should be made to reach these patients in order to raise awareness of the risk of schistosomiasis infection. This is of importance as we show, that counselled patients present faster after returning from travels to a medical center. In addition, over 40% of patients diagnosed with schistosomiasis were asymptomatic. Thus posttravel consultations with emphasis on schistosomiasis show a high chance for detecting asymptomatic infections., Einleitung: Schistosomiasis ist eine parasitäre Erkrankung von hoher Prävalenz mit über 200 Millionen betroffenen Menschen in 78 tropischen bzw. subtropischen Ländern und stellt weltweit ein massives Gesundheitsproblem dar. In nicht endemischen Ländern wird die Krankheit ebenfalls regelhaft bei Reisenden bzw. Reiserückkehrern oder Migranten aus endemischen Ländern diagnostiziert. Methodik: Das europäische Netzwerk TropNet – European Network for Tropical Medicine and Travel Health führte zwischen 1997 und 2010 eine Surveillance Studie bezüglich importierter Schistosomiasis in Europa durch. Es wurden klinische und demographische Daten von Reiserückkehrern und Migranten erfasst. Das Ziel der Analyse war die Gewinnung von klinischen und epidemiologischen Daten bei nach Europa importierter Schistosomiasis mit besonderer Berücksichtigung geographischer Informationen des Infektionsortes. Darüber hinaus war die Identifikation von Risikofaktoren für eine Infektion ein weiteres Ziel der Studie. Ergebnisse: Insgesamt wurden 1465 nach Europa importierte Schistosomiasis Fälle analysiert. 486 (33%) Fälle wurden bei europäischen Reisenden, 231 (16%) bei dauerhaft im Ausland lebenden Europäern (‚Expatriaten’) und 748 (51%) bei nicht-Europäern gefunden. 18.6% der Patienten hatten vor Reisebeginn eine Reiseberatung erhalten; in Europa-lebende Migranten, die Freunde oder Verwandte in endemischen Gebieten besuchten (VFRs) nahmen nahezu keine Reiseberatung in Anspruch. Annähernd alle (95%) der Infektionen erfolgten auf dem afrikanischen Kontinent. Europäische Reisende infizierten sich hauptsächlich in Ostafrika und einigen Ländern Westafrikas, wohingegen Migranten ein verteiltes Bild aus ganz Afrika zeigten mit einem Hoch in Westafrika. Schistosoma mansoni wurde in 570 (39%) und Schistosoma haematobium in 318 (22%) Fällen identifiziert. Insgesamt zeigten 57.5% der Patienten Symptome. Akute Symptome waren in 27% vorhanden, was mit einer früheren Vorstellung in einer tropenmedizinischen Einrichtung innerhalb von 3 Monaten nach Rückkehr assoziiert war. Mikroskopie und Serologie waren die wichtigsten Diagnosemethoden – bei symptomatischen sowie asymptomatischen Patienten. Schlussfolgerung: Schistosomiasis stellt eine relevante reisebezogene bzw. importierte Infektion bei Reisenden und Migranten aus Afrika nach Europa dar. Die Inanspruchnahme einer Reiseberatung war bei allen Reisenden gering, insbesondere bei VFR Patienten. Daher sollten Bemühungen unternommen werden Patienten vor Reisebeginn über das Schistosomiasis-Risiko aufzuklären. Dies ist von Bedeutung, da wir zeigen konnten, dass sich informierte Patienten schneller in tropenmedizinischen Einrichtungen vorstellen. Zudem waren über 40% der Reisenden asymptomatisch. Dies macht eine medizinische Nachuntersuchung mit besonderer Berücksichtigung von Schistosomiasis sinnvoll, insbesondere in Anbetracht des hohen Potenzials eine asymptomatische Infektion via Mikroskopie oder Serologie zu finden.

Published
2018

20. Impact of dexamethasone on SARS-CoV-2 concentration kinetics and antibody response in hospitalized COVID-19 patients: results from a prospective observational study

Author

Hippenstiel, Stefan, Haenel, Sascha S., Mittermaier, Mirja, Steinbeis, Fridolin, Lingscheid, Tilman, Temmesfeld-Wollbrück, Bettina, Zoller, Thomas, Müller-Redetzky, Holger, Uhrig, Alexander, Grund, Daniel, Ruwwe-Glösenkamp, Christoph, Stegemann, Miriam S., Heim, Katrin M., Hübner, Ralf H., Opitz, Bastian, Eckardt, Kai-Uwe, Möckel, Martin, Balzer, Felix, Spies, Claudia, Weber-Carstens, Steffen, Tacke, Frank, Dang-Heine, Chantip, Hummel, Michael, Schwanitz, Georg, Behrens, Uwe D., Rönnefarth, Maria, Schmidt, Sein, Krannich, Alexander, von Kalle, Christof, Jürgens, Linda, Kleinschmidt, Malte, Denker, Sophy, Pfeiffer, Moritz, Pascual-Leone, Belén Millet, Mrziglod, Luisa, Machleidt, Felix, Albus, Sebastian, Bremer, Felix, Doehn, Jan-Moritz, Andermann, Tim, Garcia, Carmen, Knape, Philipp, Krause, Philipp M., Lechtenberg, Liron, Li, Yaosi, Pergantis, Panagiotis, Jacobi, Till, Ritter, Teresa, Yedikat, Berna, Pfannkuch, Lennart, Zobel, Christian, Kellermann, Ute, Fieberg, Susanne, Bosquillon de Jarcy, Laure, Wetzel, Anne, Tabeling, Christoph, Brack, Markus C., Müller-Plathe, Moritz, Kruse, Jan M., Zickler, Daniel, Edel, Andreas, Stier, Britta, Körner, Roland, Müller, Nils B., Enghard, Philipp, Stubbemann, Paula, Olk, Nadine, Koch, Willi M., Horn, Alexandra, Stoyanova, Katrin K., Zvorc, Saskia, Kretzler, Lucie, Meyer-Arndt, Lil A., Li, Linna, Wirsching, Isabelle, Treue, Denise, Briesemeister, Dana, Schlesinger, Jenny, Sawitzki, Birgit, Bardtke, Lara, Pohl, Kai, Georg, Philipp, Wendisch, Daniel, Hiller, Anna L., Brumhard, Sophie, Schmidt, Marie Luisa, Meiners, Leonie, Tscheak, Patricia, Mühlemann, Barbara, Thibeault, Charlotte, Hillus, David, Helbig, Elisa T., Lippert, Lena J., Tober-Lau, Pinkus, Schwarz, Tatjana, Müller, Marcel A., Witzenrath, Martin, Suttorp, Norbert, Sander, Leif E., Drosten, Christian, Jones, Terry C., Corman, Victor M., and Kurth, Florian

Published
2021
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21. Severe malaria in Europe : an 8-year multi-centre observational study

Author

Kurth, Florian Michael, Develoux, Michel, Mechain, Matthieu, Malvy, Denis, Clerinx, Jan, Antinori, Spinello, Gjørup, Ida E., Gascon, Joaquím, Mørch, Kristine, Nicastri, Emanuele, Ramharter, Michael, Bartoloni, Alessandro, Visser, Leo, Rolling, Thierry, Zanger, Philipp, Calleri, Guido, Salas‑Coronas, Joaquín, Nielsen, Henrik, Just‑Nübling, Gudrun, Neumayr, Andreas, Hachfeld, Anna, Schmid, Matthias L., Antonini, Pietro, Lingscheid, Tilman, Kern, Peter, Kapaun, Annette, Cunha, José Saraiva da, Pongratz, Peter, Soriano‑Arandes, Antoni, Schunk, Mirjam, Suttorp, Norbert, Hatz, Christoph, Zoller, Thomas, Kurth, Florian Michael, Develoux, Michel, Mechain, Matthieu, Malvy, Denis, Clerinx, Jan, Antinori, Spinello, Gjørup, Ida E., Gascon, Joaquím, Mørch, Kristine, Nicastri, Emanuele, Ramharter, Michael, Bartoloni, Alessandro, Visser, Leo, Rolling, Thierry, Zanger, Philipp, Calleri, Guido, Salas‑Coronas, Joaquín, Nielsen, Henrik, Just‑Nübling, Gudrun, Neumayr, Andreas, Hachfeld, Anna, Schmid, Matthias L., Antonini, Pietro, Lingscheid, Tilman, Kern, Peter, Kapaun, Annette, Cunha, José Saraiva da, Pongratz, Peter, Soriano‑Arandes, Antoni, Schunk, Mirjam, Suttorp, Norbert, Hatz, Christoph, and Zoller, Thomas

Abstract

Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up t

Published
2017

22. Severe malaria in Europe: an 8-year multi-centre observational study

Author

Kurth, Florian, primary, Develoux, Michel, additional, Mechain, Matthieu, additional, Malvy, Denis, additional, Clerinx, Jan, additional, Antinori, Spinello, additional, Gjørup, Ida E., additional, Gascon, Joaquím, additional, Mørch, Kristine, additional, Nicastri, Emanuele, additional, Ramharter, Michael, additional, Bartoloni, Alessandro, additional, Visser, Leo, additional, Rolling, Thierry, additional, Zanger, Philipp, additional, Calleri, Guido, additional, Salas-Coronas, Joaquín, additional, Nielsen, Henrik, additional, Just-Nübling, Gudrun, additional, Neumayr, Andreas, additional, Hachfeld, Anna, additional, Schmid, Matthias L., additional, Antonini, Pietro, additional, Lingscheid, Tilman, additional, Kern, Peter, additional, Kapaun, Annette, additional, da Cunha, José Saraiva, additional, Pongratz, Peter, additional, Soriano-Arandes, Antoni, additional, Schunk, Mirjam, additional, Suttorp, Norbert, additional, Hatz, Christoph, additional, and Zoller, Thomas, additional

Published
2017
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23. In vitro activity of immunosuppressive drugs against Plasmodium falciparum

Author

Veletzky, Luzia, Rehman, Khalid, Lingscheid, Tilman, Poeppl, Wolfgang, Loetsch, Felix, Burgmann, Heinz, and Ramharter, Michael

Subjects
Sirolimus, Research, Plasmodium falciparum, Drug Repositioning, Mycophenolic Acid, Immunosuppressives, Antimalarials, Inhibitory Concentration 50, Infectious Diseases, Parasitic Sensitivity Tests, parasitic diseases, Humans, Parasitology, Rapamycin, Everolimus, Immunosuppressive Agents
Abstract

Background Solid organ transplant recipients are particularly vulnerable for infectious diseases due to prolonged immunosuppressive treatment. Residents of endemic regions and travellers may be exposed to malaria and may, therefore, require prolonged antimalarial chemoprophylaxis. The hypothesis of this study was that certain immunosuppressive drugs may exert clinically relevant anti-malarial activity. It was therefore designed to assess the intrinsic anti-malarial activity of everolimus, mycophenolic acid, and rapamycin against Plasmodium falciparum in an in vitro model. Methods Three laboratory adapted clones of P. falciparum and two isolates were used to assess the potential of mycophenolic acid, rapamycin and everolimus to inhibit in vitro growth of P. falciparum. The standard histidine rich protein 2 assay was employed and inhibitory drug concentrations (IC) were computed by non-linear regression analysis. Results All drugs were associated with complete inhibition of P. falciparum growth in in vitro assays. Mycophenolic acid demonstrated IC50 and IC90 values of 5.4 μmol/L and 15.3 μmol/L. Rapamycin inhibited P. falciparum growth at 7.2 μmol/L (IC50) and 12.5 μmol/L (IC90), respectively. Finally, everolimus displayed IC50 and IC90 values of 6.2 μmol/L and 11.5 μmol/L. There was no difference in in vitro activity against chloroquine sensitive or chloroquine resistant parasites. Conclusions All immunosuppressive drugs evaluated in this in vitro study demonstrated activity against P. falciparum. Inhibitory concentrations of mycophenolic acid are within clinically achievable plasma concentrations when used in solid organ transplant recipients. Further in vivo evaluation of mycophenolic acid either alone or in combination regimens may prove promising for the concomitant prevention of P. falciparum in solid organ transplant recipients living or travelling in malaria endemic regions.

Published
2014

24. Hemolysis after Oral Artemisinin Combination Therapy for UncomplicatedPlasmodium falciparumMalaria

Author

Kurth, Florian, primary, Lingscheid, Tilman, additional, Steiner, Florian, additional, Stegemann, Miriam S., additional, Bélard, Sabine, additional, Menner, Nikolai, additional, Pongratz, Peter, additional, Kim, Johanna, additional, von Bernuth, Horst, additional, Mayer, Beate, additional, Damm, Georg, additional, Seehofer, Daniel, additional, Salama, Abdulgabar, additional, Suttorp, Norbert, additional, and Zoller, Thomas, additional

Published
2016
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25. A diagnostic predicament: activated sarcoidosis or pulmonary histoplasmosis. A case report

Author

Lingscheid, Tilman, primary, von Heinz, Marie, additional, Klages, Birgit, additional, Rickerts, Volker, additional, Tintelnot, Kathrin, additional, Gerhold, Manuela, additional, Oestmann, Jörg‐Wilhelm, additional, Becker, Markus, additional, Temmesfeld‐Wollbrück, Bettina, additional, Suttorp, Norbert, additional, and Hübner, Ralf‐Harto, additional

Published
2015
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28. Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data.

Author

Lingscheid, Tilman, Kurth, Florian, Clerinx, Jan, Marocco, Stefania, Trevino, Begoña, Schunk, Mirjam, Muñoz, José, Gjørup, Ida E., Jelinek, Tomas, Develoux, Michel, Fry, Graham, Jänisch, Thomas, Schmid, Matthias L., Bouchaud, Olivier, Puente, Sabino, Zammarchi, Lorenzo, Mørch, Kristine, Björkman, Anders, Siikamäki, Heli, and Neumayr, Andreas

Published
2017
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29. A diagnostic predicament: activated sarcoidosis or pulmonary histoplasmosis. A case report.

Author

Lingscheid, Tilman, von Heinz, Marie, Klages, Birgit, Rickerts, Volker, Tintelnot, Kathrin, Gerhold, Manuela, Oestmann, Jörg‐Wilhelm, Becker, Markus, Temmesfeld‐Wollbrück, Bettina, Suttorp, Norbert, and Hübner, Ralf‐Harto

Subjects
*SARCOIDOSIS, *LUNG diseases, *HISTOPLASMOSIS, *SEROLOGY, *MICROBIOLOGY, *BRONCHOSCOPY
Abstract

We report a case of a 41-year-old man presenting with persisting fevers over 2 weeks. The patient had spent 4 weeks in Central America. He was in control of a stable stage II sarcoidosis. Laboratory and various microbiological tests as well as chest radiography led to no diagnosis. Activated sarcoidosis was hypothesized as the most likely diagnosis. However, we considered an infectious process as a differential diagnosis, in detail, the travel history imposed histoplasmosis. Chest-CT documented localized interstitial consolidations. Bronchoscopy with bronchoalveolar lavage (BAL) and biopsy was performed. Results of BAL fluid, biopsy, distinct sarcoidosis serum markers and a borderline positive histoplasmosis-serology yielded in a diagnostic dilemma as no distinct diagnosis was drawable. After the patient was already started on a prednisolone trial, the final diagnosis - pulmonary histoplasmosis - could be achieved via positive culture and PCR out of the BAL fluid. This case shows the difficult differentiation between an acute exacerbation of a chronic pulmonary disease and a concomitant infection, which was especially aggravated in this case as the histoplasmosis masqueraded an acute picture of sarcoidosis. [ABSTRACT FROM AUTHOR]

Published
2017
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30. Efficacy of Fosfomycin Compared to Vancomycin in Treatment of Implant-Associated Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rats

Author

Poeppl, Wolfgang, primary, Lingscheid, Tilman, additional, Bernitzky, Dominik, additional, Schwarze, Uwe Y., additional, Donath, Oliver, additional, Perkmann, Thomas, additional, Kozakowski, Nicolas, additional, Plasenzotti, Roberto, additional, Reznicek, Gottfried, additional, and Burgmann, Heinz, additional

Published
2014
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32. Hemolysis after Oral Artemisinin Combination Therapy for Uncomplicated Plasmodium falciparum Malaria.

Author

Kurth, Florian, Lingscheid, Tilman, Steiner, Florian, Stegemann, Miriam S., Bélard, Sabine, Menner, Nikolai, Pongratz, Peter, Kim, Johanna, von Bernuth, Horst, Mayer, Beate, Damm, Georg, Seehofer, Daniel, Salama, Abdulgabar, Suttorp, Norbert, and Zoller, Thomas

Subjects
*HEMOLYSIS & hemolysins, *ARTEMISININ, *ANTIMALARIALS, *ANTIGEN-antibody reactions, *IMMUNITY, *HEMOGLOBINS, *DRUG therapy for malaria, *ANEMIA, *COMBINATION drug therapy, *COMPARATIVE studies, *ETHANOLAMINES, *HYDROCARBONS, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *ORAL drug administration, *QUINOLINE, *RESEARCH, *EVALUATION research, *THERAPEUTICS
Abstract

Episodes of delayed hemolysis 2-6 weeks after treatment of severe malaria with intravenous artesunate have been described. We performed a prospective observational study of patients with uncomplicated malaria to investigate whether posttreatment hemolysis also occurs after oral artemisinin-based combination therapy. Eight of 20 patients with uncomplicated malaria who were given oral artemisinin-based combination therapy met the definition of posttreatment hemolysis (low haptoglobin level and increased lactate dehydrogenase level on day 14). Five patients had hemolysis persisting for 1 month. Patients with posttreatment hemolysis had a median decrease in hemoglobin level of 1.3 g/dL (interquartile range 0.3-2.0 g/dL) in the posttreatment period, and patients without posttreatment hemolysis had a median increase of 0.3 g/dL (IQR -0.1 to 0.7 g/dL; p = 0.002). These findings indicate a need for increased vigilance for hemolytic events in malaria patients, particularly those with predisposing factors for anemia. [ABSTRACT FROM AUTHOR]

Published
2016
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33. Low nasal carriage of drug-resistant bacteria among medical students in Vienna.

Author

Gualdoni, Guido A., Lingscheid, Tilman, Tobudic, Selma, and Burgmann, Heinz

Subjects
*CARRIER state (Communicable diseases), *DRUG resistance in microorganisms, *HOST-bacteria relationships, *MEDICAL protocols, *MEDICAL students, *NOSE, *METHICILLIN-resistant staphylococcus aureus
Abstract

Background: Multi-drug resistant bacteria are increasing and remain a major public health challenge worldwide. In order to understand the potential role of medical students as a reservoir for circulating pathogenic bacteria and their transmission, we analysed the nasal colonisation among 86 clinically exposed medical students of the Medical University of Vienna, which is integrated into General Hospital of Vienna Methods: Nasal swabs obtained from 79 students were eligible for further analysis. Nasal swabs were analysed for Gram-positive and Gramnegative bacteria with special emphasis onmethicillin-resistant Staphyl ococcus aureus. Results: 25.3% of participants were positive for Staphylococcus aureus colonization; none of the isolates showed methicillin-resistance or expression of Pantoin-Valentine-leukocidin. However, 2.5% were positive for methicillin-resistant Staphylococcus epidermidis. No participant showed Streptococcus pneumoniae colonisation. Furthermore, 10.1% of the samples displayed growth of Gram-negative bacteria, yet none showed any relevant drug-resistance. Conclusion: In conclusion, our investigation did not reveal any clinically relevant multi-drug resistant bacterial colonisation among clinically exposed medical students in Vienna. This might be explained by well-established hygienic precautions or comparably low circulation of resistant bacteria. [ABSTRACT FROM AUTHOR]

Published
2012
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34. Daptomycin plus Fosfomycin, a Synergistic Combination in Experimental Implant-Associated Osteomyelitis Due to Methicillin-Resistant Staphylococcus aureusin Rats

Author

Lingscheid, Tilman, Poeppl, Wolfgang, Bernitzky, Dominik, Veletzky, Luzia, Kussmann, Manuel, Plasenzotti, Roberto, and Burgmann, Heinz

Abstract

ABSTRACTThe aim of this study was to evaluate the combination of daptomycin and fosfomycin in experimental chronic implant-associated osteomyelitis due to methicillin-resistant Staphylococcus aureus(MRSA). Infection was induced in the tibiae of rats by the insertion of a bacterial inoculum (1 to 5 × 108CFU/ml) of a clinical MRSA isolate and a titanium wire. Four weeks after infection, each animal was assigned to a treatment group: daptomycin monotherapy at 60 mg/kg of body weight once daily (n= 10), fosfomycin monotherapy at 40 mg/kg once daily (n= 10), or daptomycin and fosfomycin combined at 60 mg/kg and 40 mg/kg, respectively, once daily (n= 9). Ten animals were left untreated. After a 3-week treatment period, the animals were euthanized, and the infected tibiae and implants were processed for quantitative bacterial cultures. The bacterial cultures from bones were positive for MRSA in all animals in the untreated group, the daptomycin group, and the fosfomycin group, with median bacterial counts of 2.34 × 106CFU/g bone, 1.57 × 106CFU/g bone, and 3.48 × 102CFU/g bone, respectively. In the daptomycin-fosfomycin group, 6 out of 9 animals were positive for MRSA, with a median count of 7.92 CFU/g bone. Bacterial cultures derived from the titanium wires were negative in the fosfomycin- and daptomycin-fosfomycin-treated groups. Based on bacterial counts in bones, treatment with daptomycin-fosfomycin was statistically significantly superior to all that of the other groups (P≤ 0.003). Fosfomycin was superior to daptomycin and no treatment (P< 0.0001). No development of resistance was observed in any treatment arm. The combination of daptomycin and fosfomycin demonstrated synergism against MRSA in experimental implant-associated osteomyelitis.

Published
2014
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35. Efficacy of Fosfomycin Compared to Vancomycin in Treatment of Implant-Associated Chronic Methicillin-Resistant Staphylococcus aureusOsteomyelitis in Rats

Author

Poeppl, Wolfgang, Lingscheid, Tilman, Bernitzky, Dominik, Schwarze, Uwe Y., Donath, Oliver, Perkmann, Thomas, Kozakowski, Nicolas, Plasenzotti, Roberto, Reznicek, Gottfried, and Burgmann, Heinz

Abstract

ABSTRACTFosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistant Staphylococcus aureus(MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 μl of a suspension containing 1 × 108to 5 × 108CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n= 11) or 75 mg/kg fosfomycin intraperitoneally once daily (n= 10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29 × 106CFU/g of bone) and the vancomycin group (median, 3.03 × 105CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42 × 102and 1.51 × 103CFU/g of bone). Vancomycin was superior to the no-drug control (P= 0.002), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). The cultures from the wires were positive in all untreated animals (median, 2.5 × 103CFU/implant), in 10 animals in the vancomycin group (median, 1.15 × 103CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P= 0.324), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.

Published
2014
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37. A proteomic survival predictor for COVID-19 patients in intensive care.

Author

Demichev V, Tober-Lau P, Nazarenko T, Lemke O, Kaur Aulakh S, Whitwell HJ, Röhl A, Freiwald A, Mittermaier M, Szyrwiel L, Ludwig D, Correia-Melo C, Lippert LJ, Helbig ET, Stubbemann P, Olk N, Thibeault C, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Spies C, Edel A, Müller NB, Enghard P, Zelezniak A, Bellmann-Weiler R, Weiss G, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Müller-Redetzky H, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, Kurth F, and Ralser M

Abstract

Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care., Competing Interests: The authors declare no competing interests. Author John F. Timms was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge., (Copyright: © 2022 Demichev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2022
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38. Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study.

Author

Thibeault C, Mühlemann B, Helbig ET, Mittermaier M, Lingscheid T, Tober-Lau P, Meyer-Arndt LA, Meiners L, Stubbemann P, Haenel SS, Bosquillon de Jarcy L, Lippert L, Pfeiffer M, Stegemann MS, Roehle R, Wiebach J, Hippenstiel S, Zoller T, Müller-Redetzky H, Uhrig A, Balzer F, von Kalle C, Suttorp N, Jones TC, Drosten C, Witzenrath M, Sander LE, Corman VM, and Kurth F

Subjects
COVID-19 therapy, Cohort Studies, Germany epidemiology, Hospitalization, Humans, Hypertension complications, Kinetics, Prospective Studies, Respiration, Artificial, Risk Factors, Tertiary Care Centers, Time Factors, Viral Load, Virus Shedding, COVID-19 epidemiology, COVID-19 virology, SARS-CoV-2 physiology
Abstract

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course., Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed., Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients., Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19., (© 2021. The Author(s).)

Published
2021
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