TY - JOUR A1 - Kippnich, Maximilian A1 - Kippnich, Uwe A1 - Erhard, Harald A1 - Meybohm, Patrick A1 - Wurmb, Thomas T1 - Weiterentwicklung im Katastrophenschutz: Ziel, Strategie und Taktik am Beispiel der Hochwasserkatastrophe 2021 im Ahrtal BT - Lessons learned aus Sicht der Medizinischen Task Force 47 (Unterfranken) JF - Notfall + Rettungsmedizin N2 - Hintergrund und Fragestellung Im Rahmen der überörtlichen Katastrophenhilfe war die Medizinische Task Force 47 (Unterfranken) im Juli 2021 bei der Hochwasserkatastrophe in Rheinland-Pfalz (Ahrtal) im Einsatz. Mit dem Ziel, mögliche Verbesserungen im Katastrophenschutz aus Sicht einer überregionalen Einheit aus dem Einsatz ableiten zu können, wurde dieser wissenschaftlich evaluiert und die Erkenntnisse in einen übergeordneten Kontext gesetzt. Material und Methoden Nach Definition eines konkreten Auswerteprozesses wurden durch ein interdisziplinäres Expertengremium Einsatzunterlagen und relevante Konzepte des Bayerischen Roten Kreuzes gesichtet. Auf dieser Basis wurden Strategien und Taktiken entwickelt, um die vordefinierten Ziele zu erreichen. Ergebnisse Die Leistungsfähigkeit der Einsatzeinheiten könnte durch moderne Einsatzmittel (E-Bike, Drohnen, hochgeländegängige Fahrzeuge) gesteigert werden. Zur Erhöhung der Reaktionsfähigkeit könnten neue Schnell-Einsatz-Gruppen (SEG) erforderlich sein, die als Teil von BOS-übergreifenden Erkundungseinheiten agieren und in unwegsamen Geländen autark Einsatzaufträge abarbeiten können (SEG Erkundung und SEG Gelände-Infrastruktur-Logistik-Transport). Die taktischen Einheiten könnten in die regionale und überregionale Katastrophenhilfe eingebunden und synchronisiert werden. Diskussion Für den weitestgehend ehrenamtlich organisierten Katastrophenschutz in Deutschland könnte es in Zukunft erschwert sein, die Vielzahl möglicher modernster Einsatzmittel im hochkomplexen Umfeld einer Katastrophe sicher einsetzen zu können. Eine Teilprofessionalisierung durch hauptamtliche Führungs- und Einsatzkräfte könnte eine Lösung hierfür sein. N2 - Objectives In July 2021, the Medical Task Force 47 was deployed to the flood disaster in western Germany as part of the cross-regional disaster relief system. With the aim of deriving possible improvements in disaster management, it was scientifically evaluated. The focus of this study was the strategy to build up and to maintain a responsive and efficient rescue system. Materials and methods After defining an evaluation process, an interdisciplinary panel of experts reviewed operational documents and relevant concepts of the Bavarian Red Cross. Based on these, strategies and tactics were developed to achieve predefined goals. Results The performance of the emergency units could be increased by modern vehicles and equipment (eBikes, drones, all-terrain vehicles). To improve the response capability, new rapid response groups could be required that can take over the function of an advance command and can process mission assignments in impassable terrain autonomously. These could be integrated and synchronized into regional and cross-regional disaster relief. Conclusion In future, it could be difficult for Germany’s largely volunteer-organised disaster management to safely deploy the multitude of possible state-of-the-art resources in the highly complex environment of a disaster. Partial professionalization by full-time command and control staff could be one solution for this problem. T2 - Further developments in disaster control: goal, strategy and tactic using the example of the 2021 flood disaster in the Ahr valley: lessons learned from the perspective of the Medical Task Force 47 (Lower Franconia) KW - Hochwasser KW - Sturzflut KW - Katastrophenschutz KW - Medizinische Task Force KW - Kritische Infrastruktur KW - flooding KW - sudden flood KW - civil protection KW - medical task force KW - critical infrastructure Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-346737 SN - 1434-6222 ER - TY - JOUR A1 - Bergauer, Lisa A1 - Akbas, Samira A1 - Braun, Julia A1 - Ganter, Michael T. A1 - Meybohm, Patrick A1 - Hottenrott, Sebastian A1 - Zacharowski, Kai A1 - Raimann, Florian J. A1 - Rivas, Eva A1 - López-Baamonde, Manuel A1 - Spahn, Donat R. A1 - Noethiger, Christoph B. A1 - Tscholl, David W. A1 - Roche, Tadzio R. T1 - Visual Blood, visualisation of blood gas analysis in virtual reality, leads to more correct diagnoses: a computer-based, multicentre, simulation study JF - Bioengineering N2 - Interpreting blood gas analysis results can be challenging for the clinician, especially in stressful situations under time pressure. To foster fast and correct interpretation of blood gas results, we developed Visual Blood. This computer-based, multicentre, noninferiority study compared Visual Blood and conventional arterial blood gas (ABG) printouts. We presented six scenarios to anaesthesiologists, once with Visual Blood and once with the conventional ABG printout. The primary outcome was ABG parameter perception. The secondary outcomes included correct clinical diagnoses, perceived diagnostic confidence, and perceived workload. To analyse the results, we used mixed models and matched odds ratios. Analysing 300 within-subject cases, we showed noninferiority of Visual Blood compared to ABG printouts concerning the rate of correctly perceived ABG parameters (rate ratio, 0.96; 95% CI, 0.92–1.00; p = 0.06). Additionally, the study revealed two times higher odds of making the correct clinical diagnosis using Visual Blood (OR, 2.16; 95% CI, 1.42–3.29; p < 0.001) than using ABG printouts. There was no or, respectively, weak evidence for a difference in diagnostic confidence (OR, 0.84; 95% CI, 0.58–1.21; p = 0.34) and perceived workload (Coefficient, 2.44; 95% CI, −0.09–4.98; p = 0.06). This study showed that participants did not perceive the ABG parameters better, but using Visual Blood resulted in more correct clinical diagnoses than using conventional ABG printouts. This suggests that Visual Blood allows for a higher level of situation awareness beyond individual parameters’ perception. However, the study also highlighted the limitations of today’s virtual reality headsets and Visual Blood. KW - virtual reality KW - blood gas analysis KW - data display KW - point-of-care KW - situation awareness KW - user-centred design KW - diagnostic correctness Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-310979 SN - 2306-5354 VL - 10 IS - 3 ER - TY - JOUR A1 - Schweiger, Giovanna A1 - Malorgio, Amos A1 - Henckert, David A1 - Braun, Julia A1 - Meybohm, Patrick A1 - Hottenrott, Sebastian A1 - Froehlich, Corinna A1 - Zacharowski, Kai A1 - Raimann, Florian J. A1 - Piekarski, Florian A1 - Noethiger, Christoph B. A1 - Spahn, Donat R. A1 - Tscholl, David W. A1 - Roche, Tadzio R. T1 - Visual Blood, a 3D animated computer model to optimize the interpretation of blood gas analysis JF - Bioengineering N2 - Acid–base homeostasis is crucial for all physiological processes in the body and is evaluated using arterial blood gas (ABG) analysis. Screens or printouts of ABG results require the interpretation of many textual elements and numbers, which may delay intuitive comprehension. To optimise the presentation of the results for the specific strengths of human perception, we developed Visual Blood, an animated virtual model of ABG results. In this study, we compared its performance with a conventional result printout. Seventy physicians from three European university hospitals participated in a computer-based simulation study. Initially, after an educational video, we tested the participants’ ability to assign individual Visual Blood visualisations to their corresponding ABG parameters. As the primary outcome, we tested caregivers’ ability to correctly diagnose simulated clinical ABG scenarios with Visual Blood or conventional ABG printouts. For user feedback, participants rated their agreement with statements at the end of the study. Physicians correctly assigned 90% of the individual Visual Blood visualisations. Regarding the primary outcome, the participants made the correct diagnosis 86% of the time when using Visual Blood, compared to 68% when using the conventional ABG printout. A mixed logistic regression model showed an odds ratio for correct diagnosis of 3.4 (95%CI 2.00–5.79, p < 0.001) and an odds ratio for perceived diagnostic confidence of 1.88 (95%CI 1.67–2.11, p < 0.001) in favour of Visual Blood. A linear mixed model showed a coefficient for perceived workload of −3.2 (95%CI −3.77 to −2.64) in favour of Visual Blood. Fifty-one of seventy (73%) participants agreed or strongly agreed that Visual Blood was easy to use, and fifty-five of seventy (79%) agreed that it was fun to use. In conclusion, Visual Blood improved physicians’ ability to diagnose ABG results. It also increased perceived diagnostic confidence and reduced perceived workload. This study adds to the growing body of research showing that decision-support tools developed around human cognitive abilities can streamline caregivers’ decision-making and may improve patient care. KW - blood gas analysis KW - medical devices KW - point-of-care-testing KW - situational awareness KW - technology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304150 SN - 2306-5354 VL - 10 IS - 3 ER - TY - JOUR A1 - Lotz, Christopher A1 - Notz, Quirin A1 - Kranke, Peter A1 - Kredel, Markus A1 - Meybohm, Patrick T1 - Unconventional approaches to mechanical ventilation - step-by-step through the COVID-19 crisis JF - Critical Care N2 - No abstract available. KW - COVID 19 KW - mechanical ventilation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229868 VL - 24 ER - TY - JOUR A1 - Riemer, Manuel A1 - Kranke, Peter A1 - Helf, Antonia A1 - Mayer, Debora A1 - Popp, Maria A1 - Schlesinger, Tobias A1 - Meybohm, Patrick A1 - Weibel, Stephanie T1 - Trial registration and selective outcome reporting in 585 clinical trials investigating drugs for prevention of postoperative nausea and vomiting JF - BMC Anesthesiology N2 - Background: Selective outcome reporting in clinical trials introduces bias in the body of evidence distorting clinical decision making. Trial registration aims to prevent this bias and is suggested by the International Committee of Medical Journal Editors (ICMJE) since 2004. Methods: The 585 randomized controlled trials (RCTs) published between 1965 and 2017 that were included in a recently published Cochrane review on antiemetic drugs for prevention of postoperative nausea and vomiting were selected. In a retrospective study, we assessed trial registration and selective outcome reporting by comparing study publications with their registered protocols according to the ‘Cochrane Risk of bias’ assessment tool 1.0. Results: In the Cochrane review, the first study which referred to a registered trial protocol was published in 2004. Of all 585 trials included in the Cochrane review, 334 RCTs were published in 2004 or later, of which only 22% (75/334) were registered. Among the registered trials, 36% (27/75) were pro- and 64% (48/75) were retrospectively registered. 41% (11/27) of the prospectively registered trials were free of selective outcome reporting bias, 22% (6/27) were incompletely registered and assessed as unclear risk, and 37% (10/27) were assessed as high risk. Major outcome discrepancies between registered and published high risk trials were a change from the registered primary to a published secondary outcome (32%), a new primary outcome (26%), and different outcome assessment times (26%). Among trials with high risk of selective outcome reporting 80% favoured at least one statistically significant result. Registered trials were assessed more often as ‘overall low risk of bias’ compared to non-registered trials (64% vs 28%). Conclusions: In 2017, 13 years after the ICMJE declared prospective protocol registration a necessity for reliable clinical studies, the frequency and quality of trial registration in the field of PONV is very poor. Selective outcome reporting reduces trustworthiness in findings of clinical trials. Investigators and clinicians should be aware that only following a properly registered protocol and transparently reporting of predefined outcomes, regardless of the direction and significance of the result, will ultimately strengthen the body of evidence in the field of PONV research in the future. KW - clinical trial KW - postoperative nausea and vomiting KW - selective outcome reporting KW - systematic review KW - trial registration Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265518 VL - 21 ER - TY - JOUR A1 - Helmer, Philipp A1 - Helf, Daniel A1 - Sammeth, Michael A1 - Winkler, Bernd A1 - Hottenrott, Sebastian A1 - Meybohm, Patrick A1 - Kranke, Peter T1 - The use of non-invasive continuous blood pressure measuring (ClearSight\(^®\)) during central neuraxial anaesthesia for caesarean section — a retrospective validation study JF - Journal of Clinical Medicine N2 - Background: The close monitoring of blood pressure during a caesarean section performed under central neuraxial anaesthesia should be the standard of safe anaesthesia. As classical oscillometric and invasive blood pressure measuring have intrinsic disadvantages, we investigated a novel, non-invasive technique for continuous blood pressure measuring. Methods: In this monocentric, retrospective data analysis, the reliability of continuous non-invasive blood pressure measuring using ClearSight\(^®\) (Edwards Lifesciences Corporation) is validated in 31 women undergoing central neuraxial anaesthesia for caesarean section. In addition, patients and professionals evaluated ClearSight\(^®\) through questioning. Results: 139 measurements from 11 patients were included in the final analysis. Employing Bland–Altman analyses, we identified a bias of −10.8 mmHg for systolic, of −0.45 mmHg for diastolic and of +0.68 mmHg for mean arterial blood pressure measurements. Pooling all paired measurements resulted in a Pearson correlation coefficient of 0.7 for systolic, of 0.67 for diastolic and of 0.75 for mean arterial blood pressure. Compensating the interindividual differences in linear regressions of the paired measurements provided improved correlation coefficients of 0.73 for systolic, of 0.9 for diastolic and of 0.89 for mean arterial blood pressure measurements. Discussion: Diastolic and mean arterial blood pressure are within an acceptable range of deviation from the reference method, according to the Association for the Advancement of Medical Instrumentation (AAMI) in the patient collective under study. Both patients and professionals prefer ClearSight\(^®\) to oscillometric blood pressure measurement in regard of comfort and handling. KW - volume clamp KW - epidural anaesthesia KW - supine hypotensive syndrome KW - ClearSight\(^®\) KW - Bland–Altman KW - Fisher Z-score transformation KW - Pearson correlation coefficient Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286042 SN - 2077-0383 VL - 11 IS - 15 ER - TY - JOUR A1 - Averdunk, Luisa A1 - Bernhagen, Jürgen A1 - Fehnle, Karl A1 - Surowy, Harald A1 - Lüdecke, Hermann-Josef A1 - Mucha, Sören A1 - Meybohm, Patrick A1 - Wieczorek, Dagmar A1 - Leng, Lin A1 - Marx, Gernot A1 - Leaf, David E. A1 - Zarbock, Alexander A1 - Zacharowski, Kai A1 - Bucala, Richard A1 - Stoppe, Christian T1 - The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery JF - Journal of Clinical Medicine N2 - Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT\(_{5–7}\) (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT\(_7\)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT\(_7\) were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT\(_7\) predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT\(_7\) was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT\(_7\) allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance. KW - acute kidney injury KW - genetic polymorphisms KW - risk prediction KW - (cardiac) surgery KW - inflammatory cytokines KW - clinical studies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213126 SN - 2077-0383 VL - 9 IS - 9 ER - TY - JOUR A1 - Kippnich, Maximilian A1 - Duempert, Maximilian A1 - Schorscher, Nora A1 - Jordan, Martin C. A1 - Kunz, Andreas S. A1 - Meybohm, Patrick A1 - Wurmb, Thomas T1 - Simultaneous treatment of trauma patients in a dual room trauma suite with integrated movable sliding gantry CT system: an observational study JF - Scientific Reports N2 - The trauma center of the University Hospital Wuerzburg has developed an advanced trauma pathway based on a dual-room trauma suite with an integrated movable sliding gantry CT-system. This enables simultaneous CT-diagnostics and treatment of two trauma patients. The focus of this study was to investigate the quality of the concept based on defined outcome criteria in this specific setting (time from arrival to initiation of CT scan: tCT; time from arrival to initiation of emergency surgery: tES). We analyzed all trauma patients admitted to the hospital’s trauma suite from 1st May 2019 through 29th April 2020. Two subgroups were defined: trauma patients, who were treated without a second trauma patient present (group 1) and patients, who were treated simultaneously with another trauma patient (group 2). Simultaneous treatment was defined as parallel arrival within a period of 20 min. Of 423 included trauma patients, 46 patients (10.9%) were treated simultaneously. Car accidents were the predominant trauma mechanism in this group (19.6% vs. 47.8%, p < 0.05). Prehospital life-saving procedures were performed with comparable frequency in both groups (intubation 43.5% vs. 39%, p = 0.572); pleural drainage 3.2% vs. 2.2%, p = 0.708; cardiopulmonary resuscitation 5% vs. 2.2%, p = 0.387). At hospital admission, patients in group 2 suffered significantly more pain (E-problem according to Advanced Trauma Life Support principles©; 29.2% vs. 45.7%, p < 0.05). There were no significant differences in the clinical treatment (emergency procedures, vasopressor and coagulant therapy, and transfusion of red blood cells). tCT was 6 (4–10) minutes (median and IQR) in group 1 and 8 (5–15.5) minutes in group 2 (p = 0.280). tES was 90 (78–106) minutes in group 1 and 99 (97–108) minutes in group 2 (p = 0.081). The simultaneous treatment of two trauma patients in a dual-room trauma suite with an integrated movable sliding gantry CT-system requires a medical, organizational, and technical concept adapted to this special setting. Despite the oftentimes serious and life-threatening injuries, optimal diagnostic and therapeutic procedures can be guaranteed for two simultaneous trauma patients at an individual medical level in consistent quality. KW - dual-room trauma suite KW - movable sliding gantry KW - CT Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299695 VL - 12 IS - 1 ER - TY - JOUR A1 - Notz, Quirin A1 - Lotz, Christopher A1 - Herrmann, Johannes A1 - Vogt, Marius A1 - Schlesinger, Tobias A1 - Kredel, Markus A1 - Muellges, Wolfgang A1 - Weismann, Dirk A1 - Westermaier, Thomas A1 - Meybohm, Patrick A1 - Kranke, Peter T1 - Severe neurological complications in critically ill COVID‑19 patients JF - Journal of Neurology N2 - No abstract available. KW - COVID-19 KW - neurological complications Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232429 SN - 0340-5354 ER - TY - JOUR A1 - Curtaz, Carolin J. A1 - Schmitt, Constanze A1 - Herbert, Saskia-Laureen A1 - Feldheim, Jonas A1 - Schlegel, Nicolas A1 - Gosselet, Fabien A1 - Hagemann, Carsten A1 - Roewer, Norbert A1 - Meybohm, Patrick A1 - Wöckel, Achim A1 - Burek, Malgorzata T1 - Serum-derived factors of breast cancer patients with brain metastases alter permeability of a human blood-brain barrier model JF - Fluids and Barriers of the CNS N2 - Background The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breast cancer into the brain is the migration of cancer cells across the blood-brain barrier (BBB). Methods We adapted and validated the CD34\(^+\) cells-derived human in vitro BBB model (brain-like endothelial cells, BLECs) to analyse the effects of patient serum on BBB properties. We collected serum samples from healthy donors, breast cancer patients with primary cancer, and breast cancer patients with, bone, visceral or cerebral metastases. We analysed cytokine levels in these sera utilizing immunoassays and correlated them with clinical data. We used paracellular permeability measurements, immunofluorescence staining, Western blot and mRNA analysis to examine the effects of patient sera on the properties of BBB in vitro. Results The BLECs cultured together with brain pericytes in transwells developed a tight monolayer with a correct localization of claudin-5 at the tight junctions (TJ). Several BBB marker proteins such as the TJ proteins claudin-5 and occludin, the glucose transporter GLUT-1 or the efflux pumps PG-P and BCRP were upregulated in these cultures. This was accompanied by a reduced paracellular permeability for fluorescein (400 Da). We then used this model for the treatment with the patient sera. Only the sera of breast cancer patients with cerebral metastases had significantly increased levels of the cytokines fractalkine (CX3CL1) and BCA-1 (CXCL13). The increased levels of fractalkine were associated with the estrogen/progesterone receptor status of the tumour. The treatment of BLECs with these sera selectively increased the expression of CXCL13 and TJ protein occludin. In addition, the permeability of fluorescein was increased after serum treatment. Conclusion We demonstrate that the CD34\(^+\) cell-derived human in vitro BBB model can be used as a tool to study the molecular mechanisms underlying cerebrovascular pathologies. We showed that serum from patients with cerebral metastases may affect the integrity of the BBB in vitro, associated with elevated concentrations of specific cytokines such as CX3CL1 and CXCL13. KW - Metastatic breast cancer KW - Blood–brain barrier KW - In vitro models KW - CX3CL1 KW - CXCL13 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229940 VL - 17 ER - TY - JOUR A1 - Schmid, Benedikt A1 - Kredel, Markus A1 - Ullrich, Roman A1 - Krenn, Katharina A1 - Lucas, Rudolf A1 - Markstaller, Klaus A1 - Fischer, Bernhard A1 - Kranke, Peter A1 - Meybohm, Patrick A1 - Zwißler, Bernhard A1 - Frank, Sandra T1 - Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS - a randomized, placebo-controlled, double-blind trial JF - Trials N2 - Background Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients. Methods This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days. Discussion The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion. Trial registration This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47. KW - acute respiratory distress syndrome KW - solnatide KW - extravascular lung water KW - pulmonary edema KW - critical care Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258783 VL - 22 IS - 1 ER - TY - JOUR A1 - Reis, Stefanie A1 - Popp, Maria A1 - Schmid, Benedikt A1 - Stegemann, Miriam A1 - Metzendorf, Maria-Inti A1 - Kranke, Peter A1 - Meybohm, Patrick A1 - Weibel, Stephanie T1 - Safety and efficacy of intermediate- and therapeutic-dose anticoagulation for hospitalised patients with COVID-19: a systematic review and meta-analysis JF - Journal of Clinical Medicine N2 - Background: COVID-19 patients are at high thrombotic risk. The safety and efficacy of different anticoagulation regimens in COVID-19 patients remain unclear. Methods: We searched for randomised controlled trials (RCTs) comparing intermediate- or therapeutic-dose anticoagulation to standard thromboprophylaxis in hospitalised patients with COVID-19 irrespective of disease severity. To assess efficacy and safety, we meta-analysed data for all-cause mortality, clinical status, thrombotic event or death, and major bleedings. Results: Eight RCTs, including 5580 patients, were identified, with two comparing intermediate- and six therapeutic-dose anticoagulation to standard thromboprophylaxis. Intermediate-dose anticoagulation may have little or no effect on any thrombotic event or death (RR 1.03, 95% CI 0.86–1.24), but may increase major bleedings (RR 1.48, 95% CI 0.53–4.15) in moderate to severe COVID-19 patients. Therapeutic-dose anticoagulation may decrease any thrombotic event or death in patients with moderate COVID-19 (RR 0.64, 95% CI 0.38–1.07), but may have little or no effect in patients with severe disease (RR 0.98, 95% CI 0.86–1.12). The risk of major bleedings may increase independent of disease severity (RR 1.78, 95% CI 1.15–2.74). Conclusions: Certainty of evidence is still low. Moderately affected COVID-19 patients may benefit from therapeutic-dose anticoagulation, but the risk for bleeding is increased. KW - anticoagulant therapy KW - coronavirus disease 2019 KW - thrombosis KW - bleeding KW - death Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252285 SN - 2077-0383 VL - 11 IS - 1 ER - TY - JOUR A1 - Nowacka-Chmielewska, Marta A1 - Grabowska, Konstancja A1 - Grabowski, Mateusz A1 - Meybohm, Patrick A1 - Burek, Malgorzata A1 - Małecki, Andrzej T1 - Running from stress: neurobiological mechanisms of exercise-induced stress resilience JF - International Journal of Molecular Sciences N2 - Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases. KW - stress KW - stress resilience KW - anxiety KW - depression KW - neuropsychiatric disorders KW - physical activity KW - exercise Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297407 SN - 1422-0067 VL - 23 IS - 21 ER - TY - JOUR A1 - Sun, Aili A1 - Blecharz-Lang, Kinga G. A1 - Małecki, Andrzej A1 - Meybohm, Patrick A1 - Nowacka-Chmielewska, Marta M. A1 - Burek, Malgorzata T1 - Role of microRNAs in the regulation of blood-brain barrier function in ischemic stroke and under hypoxic conditions in vitro JF - Frontiers in Drug Delivery N2 - The blood-brain barrier (BBB) is a highly specialized structure that separates the brain from the blood and allows the exchange of molecules between these two compartments through selective channels. The breakdown of the BBB is implicated in the development of severe neurological diseases, especially stroke and traumatic brain injury. Oxygen-glucose deprivation is used to mimic stroke and traumatic brain injury in vitro. Pathways that trigger BBB dysfunction include an imbalance of oxidative stress, excitotoxicity, iron metabolism, cytokine release, cell injury, and cell death. MicroRNAs are small non-coding RNA molecules that regulate gene expression and are emerging as biomarkers for the diagnosis of central nervous system (CNS) injuries. In this review, the regulatory role of potential microRNA biomarkers and related therapeutic targets on the BBB is discussed. A thorough understanding of the potential role of various cellular and linker proteins, among others, in the BBB will open further therapeutic options for the treatment of neurological diseases. KW - blood-brain barrier KW - microRNA KW - stroke KW - traumatic brain injury KW - tight junctions KW - transporter Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-291423 SN - 2674-0850 VL - 2 ER - TY - JOUR A1 - Fischer, Dania A1 - Thies, Fabian A1 - Awad, Omar A1 - Brat, Camilla A1 - Meybohm, Patrick A1 - Baer, Patrick C. A1 - Müller, Markus M. A1 - Urbschat, Anja A1 - Maier, Thorsten J. A1 - Zacharowski, Kai A1 - Roos, Jessica T1 - Red blood cell-derived microparticles exert no cancer promoting effects on colorectal cancer cells in vitro JF - International Journal of Molecular Sciences N2 - The biomedical consequences of allogeneic blood transfusions and the possible pathomechanisms of transfusion-related morbidity and mortality are still not entirely understood. In retrospective studies, allogeneic transfusion was associated with increased rates of cancer recurrence, metastasis and death in patients with colorectal cancer. However, correlation does not imply causation. The purpose of this study was to elucidate this empirical observation further in order to address insecurity among patients and clinicians. We focused on the in vitro effect of microparticles derived from red blood cell units (RMPs). We incubated different colon carcinoma cells with RMPs and analyzed their effects on growth, invasion, migration and tumor marker expression. Furthermore, effects on Wnt, Akt and ERK signaling were explored. Our results show RMPs do not seem to affect functional and phenotypic characteristics of different colon carcinoma cells and did not induce or inhibit Wnt, Akt or ERK signaling, albeit in cell culture models lacking tumor microenvironment. Allogeneic blood transfusions are associated with poor prognosis, but RMPs do not seem to convey tumor-enhancing effects. Most likely, the circumstances that necessitate the transfusion, such as preoperative anemia, tumor stage, perioperative blood loss and extension of surgery, take center stage. KW - transfusion KW - red blood cells KW - microparticles KW - colorectal carcinoma Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286018 SN - 1422-0067 VL - 23 IS - 16 ER - TY - JOUR A1 - Fiedler, Mascha O. A1 - Muellenbach, Ralf M. A1 - Rolfes, Caroline A1 - Lotz, Christopher A1 - Nickel, Felix A1 - Müller-Stich, Beat P. A1 - Supady, Alexander A1 - Lepper, Philipp M. A1 - Weigand, Markus A. A1 - Meybohm, Patrick A1 - Kalenka, Armin A1 - Reyher, Christian T1 - Pumpless extracorporeal hemadsorption technique (pEHAT): a proof-of-concept animal study JF - Journal of Clinical Medicine N2 - Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb\(^®\) and four Oxiris\(^®\) hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45–85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb\(^®\) blood flow [mL/min] = 4.226 × MAP [mmHg] − 3.496 (R-square 0.8133) and Oxiris\(^®\) blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb\(^®\) and Oxiris\(^®\) devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes. KW - blood purification KW - extracorporeal hemadsorption KW - cytokines KW - adsorption KW - animal model KW - immunosorbents KW - septic shock KW - endotoxin KW - extracorporeal techniques in hemadsorption therapy KW - arteriovenous extracorporeal hemadsorption technique Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297347 SN - 2077-0383 VL - 11 IS - 22 ER - TY - JOUR A1 - Feldheim, Jonas A1 - Wend, David A1 - Lauer, Mara J. A1 - Monoranu, Camelia M. A1 - Glas, Martin A1 - Kleinschnitz, Christoph A1 - Ernestus, Ralf-Ingo A1 - Braunger, Barbara M. A1 - Meybohm, Patrick A1 - Hagemann, Carsten A1 - Burek, Malgorzata T1 - Protocadherin Gamma C3 (PCDHGC3) is strongly expressed in glioblastoma and its high expression is associated with longer progression-free survival of patients JF - International Journal of Molecular Sciences N2 - Protocadherins (PCDHs) belong to the cadherin superfamily and represent the largest subgroup of calcium-dependent adhesion molecules. In the genome, most PCDHs are arranged in three clusters, α, β, and γ on chromosome 5q31. PCDHs are highly expressed in the central nervous system (CNS). Several PCDHs have tumor suppressor functions, but their individual role in primary brain tumors has not yet been elucidated. Here, we examined the mRNA expression of PCDHGC3, a member of the PCDHγ cluster, in non-cancerous brain tissue and in gliomas of different World Health Organization (WHO) grades and correlated it with the clinical data of the patients. We generated a PCDHGC3 knockout U343 cell line and examined its growth rate and migration in a wound healing assay. We showed that PCDHGC3 mRNA and protein were significantly overexpressed in glioma tissue compared to a non-cancerous brain specimen. This could be confirmed in glioma cell lines. High PCDHGC3 mRNA expression correlated with longer progression-free survival (PFS) in glioma patients. PCDHGC3 knockout in U343 resulted in a slower growth rate but a significantly faster migration rate in the wound healing assay and decreased the expression of several genes involved in WNT signaling. PCDHGC3 expression should therefore be further investigated as a PFS-marker in gliomas. However, more studies are needed to elucidate the molecular mechanisms underlying the PCDHGC3 effects. KW - glioblastoma multiforme KW - glioma KW - astrocytoma KW - recurrence KW - relapse KW - mRNA KW - protein KW - brain KW - expression KW - PCDHGC3 KW - WNT signaling Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284433 SN - 1422-0067 VL - 23 IS - 15 ER - TY - JOUR A1 - Herrmann, Johannes A1 - Müller, Kerstin A1 - Notz, Quirin A1 - Hübsch, Martha A1 - Haas, Kirsten A1 - Horn, Anna A1 - Schmidt, Julia A1 - Heuschmann, Peter A1 - Maschmann, Jens A1 - Frosch, Matthias A1 - Deckert, Jürgen A1 - Einsele, Hermann A1 - Ertl, Georg A1 - Frantz, Stefan A1 - Meybohm, Patrick A1 - Lotz, Christopher T1 - Prospective single-center study of health-related quality of life after COVID-19 in ICU and non-ICU patients JF - Scientific Reports N2 - Long-term sequelae in hospitalized Coronavirus Disease 2019 (COVID-19) patients may result in limited quality of life. The current study aimed to determine health-related quality of life (HRQoL) after COVID-19 hospitalization in non-intensive care unit (ICU) and ICU patients. This is a single-center study at the University Hospital of Wuerzburg, Germany. Patients eligible were hospitalized with COVID-19 between March 2020 and December 2020. Patients were interviewed 3 and 12 months after hospital discharge. Questionnaires included the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L), patient health questionnaire-9 (PHQ-9), the generalized anxiety disorder 7 scale (GAD-7), FACIT fatigue scale, perceived stress scale (PSS-10) and posttraumatic symptom scale 10 (PTSS-10). 85 patients were included in the study. The EQ5D-5L-Index significantly differed between non-ICU (0.78 ± 0.33 and 0.84 ± 0.23) and ICU (0.71 ± 0.27; 0.74 ± 0.2) patients after 3- and 12-months. Of non-ICU 87% and 80% of ICU survivors lived at home without support after 12 months. One-third of ICU and half of the non-ICU patients returned to work. A higher percentage of ICU patients was limited in their activities of daily living compared to non-ICU patients. Depression and fatigue were present in one fifth of the ICU patients. Stress levels remained high with only 24% of non-ICU and 3% of ICU patients (p = 0.0186) having low perceived stress. Posttraumatic symptoms were present in 5% of non-ICU and 10% of ICU patients. HRQoL is limited in COVID-19 ICU patients 3- and 12-months post COVID-19 hospitalization, with significantly less improvement at 12-months compared to non-ICU patients. Mental disorders were common highlighting the complexity of post-COVID-19 symptoms as well as the necessity to educate patients and primary care providers about monitoring mental well-being post COVID-19. KW - health care KW - public health KW - quality of life Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357174 VL - 13 ER - TY - JOUR A1 - Jung‐König, Mona A1 - Füllenbach, Christoph A1 - Murphy, Michael F. A1 - Manzini, Paola A1 - Laspina, Stefan A1 - Pendry, Kate A1 - Mühling, Jörg A1 - Wikman, Agneta A1 - Humbrecht, Catherine A1 - Rigal, Jean‐Christophe A1 - Lasocki, Sigismond A1 - Folléa, Gilles A1 - Seifried, Erhard A1 - Müller, Markus M. A1 - Geisen, Christof A1 - Aranko, Kari A1 - Zacharowski, Kai A1 - Meybohm, Patrick T1 - Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) working group JF - Vox Sanguinis N2 - Background and objectives Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce. Materials and methods To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016. Results Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron. Conclusion Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia. KW - iron deficiency KW - patient blood management KW - preoperative anaemia management Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214049 VL - 115 IS - 3 SP - 182 EP - 191 ER - TY - JOUR A1 - Notz, Quirin A1 - Schmalzing, Marc A1 - Wedekink, Florian A1 - Schlesinger, Tobias A1 - Gernert, Michael A1 - Herrmann, Johannes A1 - Sorger, Lena A1 - Weismann, Dirk A1 - Schmid, Benedikt A1 - Sitter, Magdalena A1 - Schlegel, Nicolas A1 - Kranke, Peter A1 - Wischhusen, Jörg A1 - Meybohm, Patrick A1 - Lotz, Christopher T1 - Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study JF - Frontiers in Immunology N2 - Objectives The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience. KW - Coronavirus Disease 2019 KW - acute respiratory distress syndrome KW - Severe Acute Respiratory Syndrome Coronavirus 2 KW - cytokines KW - inflammation KW - growth differentiation factor 15 KW - immune response Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212815 SN - 1664-3224 VL - 11 ER -