@article{Jung‐KoenigFuellenbachMurphyetal.2020,
  author    = {Jung-K{\"o}nig, Mona and F{\"u}llenbach, Christoph and Murphy, Michael F. and Manzini, Paola and Laspina, Stefan and Pendry, Kate and M{\"u}hling, J{\"o}rg and Wikman, Agneta and Humbrecht, Catherine and Rigal, Jean-Christophe and Lasocki, Sigismond and Foll{\´e}a, Gilles and Seifried, Erhard and M{\"u}ller, Markus M. and Geisen, Christof and Aranko, Kari and Zacharowski, Kai and Meybohm, Patrick},
  title     = {Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) working group},
  series = {Vox Sanguinis},
  volume    = {115},
  journal   = {Vox Sanguinis},
  number    = {3},
  doi       = {10.1111/vox.12872},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214049},
  pages     = {182 -- 191},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}
@article{MeybohmStraubFuellenbachetal.2020,
  author    = {Meybohm, Patrick and Straub, Niels and F{\"u}llenbach, Christoph and Judd, Leonie and Kleiner{\"u}schkamp, Adina and Taeuber, Isabel and Zacharowski, Kai and Choorapoikayil, Suma},
  title     = {Health economics of Patient Blood Management: a cost-benefit analysis based on a meta-analysis},
  series = {Vox Sanguinis},
  volume    = {115},
  journal   = {Vox Sanguinis},
  number    = {2},
  doi       = {10.1111/vox.12873},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214084},
  pages     = {182 -- 188},
  year      = {2020},
  abstract  = {Background and Objectives Patient Blood Management (PBM) is the timely application of evidence-based medical and surgical concepts designed to improve haemoglobin concentration, optimize haemostasis and minimize blood loss in an effort to improve patient outcomes. The focus of this cost-benefit analysis is to analyse the economic benefit of widespread implementation of a multimodal PBM programme. Materials and Methods Based on a recent meta-analysis including 17 studies (>235 000 patients) comparing PBM with control care and data from the University Hospital Frankfurt, a cost-benefit analysis was performed. Outcome data were red blood cell (RBC) transfusion rate, number of transfused RBC units, and length of hospital stay (LOS). Costs were considered for the following three PBM interventions as examples: anaemia management including therapy of iron deficiency, use of cell salvage and tranexamic acid. For sensitivity analysis, a Monte Carlo simulation was performed. Results Iron supplementation was applied in 3·1\%, cell salvage in 65\% and tranexamic acid in 89\% of the PBM patients. In total, applying these three PBM interventions costs €129·04 per patient. However, PBM was associated with a reduction in transfusion rate, transfused RBC units per patient, and LOS which yielded to mean savings of €150·64 per patient. Thus, the overall benefit of PBM implementation was €21·60 per patient. In the Monte Carlo simulation, the cost savings on the outcome side exceeded the PBM costs in approximately 2/3 of all repetitions and the total benefit was €1 878 000 in 100·000 simulated patients. Conclusion Resources to implement a multimodal PBM concept optimizing patient care and safety can be cost-effectively.},
  language  = {en}
}
@article{HerrmannAdamNotzetal.2020,
  author    = {Herrmann, Johannes and Adam, Elisabeth Hannah and Notz, Quirin and Helmer, Philipp and Sonntagbauer, Michael and Ungemach-Papenberg, Peter and Sanns, Andreas and Zausig, York and Steinfeldt, Thorsten and Torje, Iuliu and Schmid, Benedikt and Schlesinger, Tobias and Rolfes, Caroline and Reyher, Christian and Kredel, Markus and Stumpner, Jan and Brack, Alexander and Wurmb, Thomas and Gill-Schuster, Daniel and Kranke, Peter and Weismann, Dirk and Klinker, Hartwig and Heuschmann, Peter and R{\"u}cker, Viktoria and Frantz, Stefan and Ertl, Georg and Muellenbach, Ralf Michael and Mutlak, Haitham and Meybohm, Patrick and Zacharowski, Kai and Lotz, Christopher},
  title     = {COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study},
  series = {Frontiers in Medicine},
  volume    = {7},
  journal   = {Frontiers in Medicine},
  issn      = {2296-858X},
  doi       = {10.3389/fmed.2020.599533},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219834},
  year      = {2020},
  abstract  = {Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0\%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5\%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3\%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.},
  language  = {en}
}
@article{GabbertDillingMeybohmetal.2020,
  author    = {Gabbert, Lydia and Dilling, Christina and Meybohm, Patrick and Burek, Malgorzata},
  title     = {Deletion of Protocadherin Gamma C3 Induces Phenotypic and Functional Changes in Brain Microvascular Endothelial Cells In Vitro},
  series = {Frontiers in Pharmacology},
  volume    = {11},
  journal   = {Frontiers in Pharmacology},
  issn      = {1663-9812},
  doi       = {10.3389/fphar.2020.590144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219828},
  year      = {2020},
  abstract  = {Inflammation of the central nervous system (CNS) is associated with diseases such as multiple sclerosis, stroke and neurodegenerative diseases. Compromised integrity of the blood-brain barrier (BBB) and increased migration of immune cells into the CNS are the main characteristics of brain inflammation. Clustered protocadherins (Pcdhs) belong to a large family of cadherin-related molecules. Pcdhs are highly expressed in the CNS in neurons, astrocytes, pericytes and epithelial cells of the choroid plexus and, as we have recently demonstrated, in brain microvascular endothelial cells (BMECs). Knockout of a member of the Pcdh subfamily, PcdhgC3, resulted in significant changes in the barrier integrity of BMECs. Here we characterized the endothelial PcdhgC3 knockout (KO) cells using paracellular permeability measurements, proliferation assay, wound healing assay, inhibition of signaling pathways, oxygen/glucose deprivation (OGD) and a pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) treatment. PcdhgC3 KO showed an increased paracellular permeability, a faster proliferation rate, an altered expression of efflux pumps, transporters, cellular receptors, signaling and inflammatory molecules. Serum starvation led to significantly higher phosphorylation of extracellular signal-regulated kinases (Erk) in KO cells, while no changes in phosphorylated Akt kinase levels were found. PcdhgC3 KO cells migrated faster in the wound healing assay and this migration was significantly inhibited by respective inhibitors of the MAPK-, β-catenin/Wnt-, mTOR- signaling pathways (SL327, XAV939, or Torin 2). PcdhgC3 KO cells responded stronger to OGD and TNFα by significantly higher induction of interleukin 6 mRNA than wild type cells. These results suggest that PcdhgC3 is involved in the regulation of major signaling pathways and the inflammatory response of BMECs.},
  language  = {en}
}
@article{LotzNotzKrankeetal.2020,
  author    = {Lotz, Christopher and Notz, Quirin and Kranke, Peter and Kredel, Markus and Meybohm, Patrick},
  title     = {Unconventional approaches to mechanical ventilation - step-by-step through the COVID-19 crisis},
  series = {Critical Care},
  volume    = {24},
  journal   = {Critical Care},
  doi       = {10.1186/s13054-020-02954-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229868},
  year      = {2020},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{AverdunkBernhagenFehnleetal.2020,
  author    = {Averdunk, Luisa and Bernhagen, J{\"u}rgen and Fehnle, Karl and Surowy, Harald and L{\"u}decke, Hermann-Josef and Mucha, S{\"o}ren and Meybohm, Patrick and Wieczorek, Dagmar and Leng, Lin and Marx, Gernot and Leaf, David E. and Zarbock, Alexander and Zacharowski, Kai and Bucala, Richard and Stoppe, Christian},
  title     = {The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {9},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9092936},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213126},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}
@article{CurtazSchmittHerbertetal.2020,
  author    = {Curtaz, Carolin J. and Schmitt, Constanze and Herbert, Saskia-Laureen and Feldheim, Jonas and Schlegel, Nicolas and Gosselet, Fabien and Hagemann, Carsten and Roewer, Norbert and Meybohm, Patrick and W{\"o}ckel, Achim and Burek, Malgorzata},
  title     = {Serum-derived factors of breast cancer patients with brain metastases alter permeability of a human blood-brain barrier model},
  series = {Fluids and Barriers of the CNS},
  volume    = {17},
  journal   = {Fluids and Barriers of the CNS},
  doi       = {10.1186/s12987-020-00192-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229940},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}
@article{SchlesingerWeissbrichWedekinketal.2020,
  author    = {Schlesinger, Tobias and Weißbrich, Benedikt and Wedekink, Florian and Notz, Quirin and Herrmann, Johannes and Krone, Manuel and Sitter, Magdalena and Schmid, Benedikt and Kredel, Markus and Stumpner, Jan and D{\"o}lken, Lars and Wischhusen, J{\"o}rg and Kranke, Peter and Meybohm, Patrick and Lotz, Christpher},
  title     = {Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study},
  series = {PLoS One},
  volume    = {15, 2020},
  journal   = {PLoS One},
  number    = {11},
  doi       = {10.1371/journal.pone.0242917},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231348},
  year      = {2020},
  abstract  = {Background The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). Methods This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. Results Most patients (91\%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30\%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100\% of the cases, oropharyngeal swabs only in 77\%. Blood samples were positive in 26\% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). Conclusions COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.},
  language  = {en}
}
@article{NotzSchmalzingWedekinketal.2020,
  author    = {Notz, Quirin and Schmalzing, Marc and Wedekink, Florian and Schlesinger, Tobias and Gernert, Michael and Herrmann, Johannes and Sorger, Lena and Weismann, Dirk and Schmid, Benedikt and Sitter, Magdalena and Schlegel, Nicolas and Kranke, Peter and Wischhusen, J{\"o}rg and Meybohm, Patrick and Lotz, Christopher},
  title     = {Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.581338},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212815},
  year      = {2020},
  abstract  = {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 na{\"i}ve 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.},
  language  = {en}
}
@article{HottenrottSchlesingerHelmeretal.2020,
  author    = {Hottenrott, Sebastian and Schlesinger, Tobias and Helmer, Philipp and Meybohm, Patrick and Alkatout, Ibrahim and Kranke, Peter},
  title     = {Do small incisions need only minimal anesthesia? — anesthetic management in laparoscopic and robotic surgery},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {12},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9124058},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220039},
  year      = {2020},
  abstract  = {Laparoscopic techniques have established themselves as a major part of modern surgery. Their implementation in every surgical discipline has played a vital part in the reduction of perioperative morbidity and mortality. Precise robotic surgery, as an evolution of this, is shaping the present and future operating theatre that an anesthetist is facing. While incisions get smaller and the impact on the organism seems to dwindle, challenges for anesthetists do not lessen and could even become more demanding than in open procedures. This review focuses on the pathophysiological effects of contemporary laparoscopic and robotic procedures and summarizes anesthetic challenges and strategies for perioperative management.},
  language  = {en}
}
@article{NeefMeisenzahlKessleretal.2020,
  author    = {Neef, Vanessa and Meisenzahl, David and Kessler, Paul and Raimann, Florian J. and Piekarski, Florian and Choorapoikayil, Suma and Fleege, Christoph and Zacharowski, Kai D. and Meybohm, Patrick and Meurer, Andrea},
  title     = {Implementation of an anaemia walk-in clinic: Feasibility and preliminary data from the Orthopedic University Hospital},
  series = {Transfusion Medicine},
  volume    = {30},
  journal   = {Transfusion Medicine},
  number    = {6},
  doi       = {10.1111/tme.12740},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224594},
  pages     = {467 -- 474},
  year      = {2020},
  abstract  = {Background Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital. Objective Here, we demonstrate the implementation of an anaemia walk-in clinic at an Orthopedic University Hospital. To improve the diagnosis of iron deficiency (ID), we examined whether reticulocyte haemoglobin (Ret-He) could be a useful additional parameter. Material and Methods In August 2019, an anaemia walk-in clinic was established. Between September and December 2019, major orthopaedic surgical patients were screened for preoperative anaemia. The primary endpoint was the incidence of preoperative anaemia. Secondary endpoints included Ret-He level, red blood cell (RBC) transfusion rate, in-hospital length of stay and anaemia at hospital discharge. Results A total of 104 patients were screened for anaemia. Preoperative anaemia rate was 20.6\%. Intravenous iron was supplemented in 23 patients. Transfusion of RBC units per patient (1.7 ± 1.2 vs. 0.2 ± 0.9; p = 0.004) and hospital length of stay (13.1 ± 4.8 days vs. 10.6 ± 5.1 days; p = 0.068) was increased in anaemic patients compared to non-anaemic patients. Ret-He values were significantly lower in patients with ID anaemia (33.3 pg [28.6-40.2 pg]) compared to patients with ID (35.3 pg [28.9-38.6 pg]; p = 0.015) or patients without anaemia (35.4 pg [30.2-39.4 pg]; p = 0.001). Conclusion Preoperative anaemia is common in orthopaedic patients. Our results proved the feasibility of an anaemia walk-in clinic to manage preoperative anaemia. Furthermore, our analysis supports the use of Ret-He as an additional parameter for the diagnosis of ID in surgical patients.},
  language  = {en}
}
@article{RiemerKrankeHelfetal.2021,
  author    = {Riemer, Manuel and Kranke, Peter and Helf, Antonia and Mayer, Debora and Popp, Maria and Schlesinger, Tobias and Meybohm, Patrick and Weibel, Stephanie},
  title     = {Trial registration and selective outcome reporting in 585 clinical trials investigating drugs for prevention of postoperative nausea and vomiting},
  series = {BMC Anesthesiology},
  volume    = {21},
  journal   = {BMC Anesthesiology},
  doi       = {10.1186/s12871-021-01464-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265518},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{HerrmannNotzSchlesingeretal.2021,
  author    = {Herrmann, Johannes and Notz, Quirin and Schlesinger, Tobias and Stumpner, Jan and Kredel, Markus and Sitter, Magdalena and Schmid, Benedikt and Kranke, Peter and Schulze, Harald and Meybohm, Patrick and Lotz, Christopher},
  title     = {Point of care diagnostic of hypercoagulability and platelet function in COVID-19 induced acute respiratory distress syndrome: a retrospective observational study},
  series = {Thrombosis Journal},
  volume    = {19},
  journal   = {Thrombosis Journal},
  number    = {1},
  doi       = {10.1186/s12959-021-00293-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260739},
  year      = {2021},
  abstract  = {Background Coronavirus disease 2019 (COVID-19) associated coagulopathy (CAC) leads to thromboembolic events in a high number of critically ill COVID-19 patients. However, specific diagnostic or therapeutic algorithms for CAC have not been established. In the current study, we analyzed coagulation abnormalities with point-of-care testing (POCT) and their relation to hemostatic complications in patients suffering from COVID-19 induced Acute Respiratory Distress Syndrome (ARDS). Our hypothesis was that specific diagnostic patterns can be identified in patients with COVID-19 induced ARDS at risk of thromboembolic complications utilizing POCT. Methods This is a single-center, retrospective observational study. Longitudinal data from 247 rotational thromboelastometries (Rotem®) and 165 impedance aggregometries (Multiplate®) were analysed in 18 patients consecutively admitted to the ICU with a COVID-19 induced ARDS between March 12th to June 30th, 2020. Results Median age was 61 years (IQR: 51-69). Median PaO2/FiO2 on admission was 122 mmHg (IQR: 87-189), indicating moderate to severe ARDS. Any form of hemostatic complication occurred in 78 \% of the patients with deep vein/arm thrombosis in 39 \%, pulmonary embolism in 22 \%, and major bleeding in 17 \%. In Rotem® elevated A10 and maximum clot firmness (MCF) indicated higher clot strength. The delta between EXTEM A10 minus FIBTEM A10 (ΔA10) > 30 mm, depicting the sole platelet-part of clot firmness, was associated with a higher risk of thromboembolic events (OD: 3.7; 95 \%CI 1.3-10.3; p = 0.02). Multiplate® aggregometry showed hypoactive platelet function. There was no correlation between single Rotem® and Multiplate® parameters at intensive care unit (ICU) admission and thromboembolic or bleeding complications. Conclusions Rotem® and Multiplate® results indicate hypercoagulability and hypoactive platelet dysfunction in COVID-19 induced ARDS but were all in all poorly related to hemostatic complications..},
  language  = {en}
}
@article{NotzLotzHerrmannetal.2021,
  author    = {Notz, Quirin and Lotz, Christopher and Herrmann, Johannes and Vogt, Marius and Schlesinger, Tobias and Kredel, Markus and Muellges, Wolfgang and Weismann, Dirk and Westermaier, Thomas and Meybohm, Patrick and Kranke, Peter},
  title     = {Severe neurological complications in critically ill COVID‑19 patients},
  series = {Journal of Neurology},
  journal   = {Journal of Neurology},
  issn      = {0340-5354},
  doi       = {10.1007/s00415-020-10152-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232429},
  pages     = {1576-1579},
  year      = {2021},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{SchmidKredelUllrichetal.2021,
  author    = {Schmid, Benedikt and Kredel, Markus and Ullrich, Roman and Krenn, Katharina and Lucas, Rudolf and Markstaller, Klaus and Fischer, Bernhard and Kranke, Peter and Meybohm, Patrick and Zwißler, Bernhard and Frank, Sandra},
  title     = {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},
  series = {Trials},
  volume    = {22},
  journal   = {Trials},
  number    = {1},
  doi       = {10.1186/s13063-021-05588-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258783},
  pages     = {643},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{SchraderRieseKurlbaumetal.2021,
  author    = {Schrader, Nikolas and Riese, Thorsten and Kurlbaum, Max and Meybohm, Patrick and Kredel, Markus and Surat, G{\"u}zin and Scherf-Clavel, Oliver and Strate, Alexander and Pospiech, Andreas and Hoppe, Kerstin},
  title     = {Personalized antibiotic therapy for the critically ill: Implementation strategies and effects on clinical outcome of piperacillin therapeutic drug monitoring — a descriptive retrospective analysis},
  series = {Antibiotics},
  volume    = {10},
  journal   = {Antibiotics},
  number    = {12},
  issn      = {2079-6382},
  doi       = {10.3390/antibiotics10121452},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250052},
  year      = {2021},
  abstract  = {Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians' alertness.},
  language  = {en}
}
@article{WeibelPaceSchaeferetal.2021,
  author    = {Weibel, Stephanie and Pace, Nathan L. and Schaefer, Maximilian S. and Raj, Diana and Schlesinger, Tobias and Meybohm, Patrick and Kienbaum, Peter and Eberhart, Leopold H. J. and Kranke, Peter},
  title     = {Drugs for preventing postoperative nausea and vomiting in adults after general anesthesia: An abridged Cochrane network meta-analysis},
  series = {Journal of Evidence-Based Medicine},
  volume    = {14},
  journal   = {Journal of Evidence-Based Medicine},
  number    = {3},
  doi       = {10.1111/jebm.12429},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259470},
  pages     = {188-197},
  year      = {2021},
  abstract  = {Objective In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time needed to prepare what is now the largest Cochrane review with network meta-analysis in terms of the number of included studies and pages in its full printed form. Methods We conducted a systematic review with network meta-analyses to compare and rank single antiemetic drugs and their combinations belonging to 5HT₃-, D₂-, NK₁-receptor antagonists, corticosteroids, antihistamines, and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anesthesia. Results 585 studies (97 516 participants) testing 44 single drugs and 51 drug combinations were included. The studies' overall risk of bias was assessed as low in only 27\% of the studies. In 282 studies, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20\% compared to placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single NK1 receptor antagonists were as effective as other drug combinations. Of the 10 effective single drugs, certainty of evidence was high for aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron, while moderate for fosaprepitant and droperidol. For serious adverse events (SAEs), any adverse event (AE), and drug-class specific side effects evidence for intervention effects was mostly not convincing. Conclusions There is high or moderate evidence for at least seven single drugs preventing postoperative vomiting. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.},
  language  = {en}
}
@article{SchlesingerWeibelSteinfeldtetal.2021,
  author    = {Schlesinger, Tobias and Weibel, Stephanie and Steinfeldt, Thorsten and Sitter, Magdalena and Meybohm, Patrick and Kranke, Peter},
  title     = {Intraoperative management of combined general anesthesia and thoracic epidural analgesia: A survey among German anesthetists},
  series = {Acta Anaesthesiologica Scandinavica},
  volume    = {65},
  journal   = {Acta Anaesthesiologica Scandinavica},
  number    = {10},
  doi       = {10.1111/aas.13971},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258286},
  pages     = {1490-1496},
  year      = {2021},
  abstract  = {Background Evidence concerning combined general anesthesia (GA) and thoracic epidural analgesia (EA) is controversial and the procedure appears heterogeneous in clinical implementation. We aimed to gain an overview of different approaches and to unveil a suspected heterogeneity concerning the intraoperative management of combined GA and EA. Methods This was an anonymous survey among Members of the Scientific working group for regional anesthesia within the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) conducted from February 2020 to August 2020. Results The response rate was 38\%. The majority of participants were experienced anesthetists with high expertise for the specific regimen of combined GA and EA. Most participants establish EA in the sitting position (94\%), prefer early epidural initiation (prior to skin incision: 80\%; intraoperative: 14\%) and administer ropivacaine (89\%) in rather low concentrations (0.2\%: 45\%; 0.375\%: 30\%; 0.75\%: 15\%) mostly with an opioid (84\%) in a bolus-based mode (95\%). The majority reduce systemic opioid doses intraoperatively if EA works sufficiently (minimal systemic opioids: 58\%; analgesia exclusively via EA: 34\%). About 85\% manage intraoperative EA insufficiency with systemic opioids, 52\% try to escalate EA, and only 25\% use non-opioids, e.g. intravenous ketamine or lidocaine. Conclusions Although, consensus seems to be present for several aspects (patient's position during epidural puncture, main epidural substance, application mode), there is considerable heterogeneity regarding systemic opioids, rescue strategies for insufficient EA, and hemodynamic management, which might explain inconsistent results of previous trials and meta-analyses.},
  language  = {en}
}
@article{ReisPoppSchmidetal.2021,
  author    = {Reis, Stefanie and Popp, Maria and Schmid, Benedikt and Stegemann, Miriam and Metzendorf, Maria-Inti and Kranke, Peter and Meybohm, Patrick and Weibel, Stephanie},
  title     = {Safety and efficacy of intermediate- and therapeutic-dose anticoagulation for hospitalised patients with COVID-19: a systematic review and meta-analysis},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {1},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11010057},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252285},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@article{NotzHerrmannSchlesingeretal.2021,
  author    = {Notz, Quirin and Herrmann, Johannes and Schlesinger, Tobias and Helmer, Philipp and Sudowe, Stephan and Sun, Qian and Hackler, Julian and Roeder, Daniel and Lotz, Christopher and Meybohm, Patrick and Kranke, Peter and Schomburg, Lutz and Stoppe, Christian},
  title     = {Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS},
  series = {Nutrients},
  volume    = {13},
  journal   = {Nutrients},
  number    = {6},
  issn      = {2072-6643},
  doi       = {10.3390/nu13062113},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241112},
  year      = {2021},
  abstract  = {The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95\%) suffered from severe ARDS and 14 patients (64\%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = -0.495), PCT (r\(_s\) = -0.413), IL-6 (r\(_s\) = -0.429), IL-1β (r\(_s\) = -0.440) and IL-10 (r\(_s\) = -0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.},
  language  = {en}
}
@article{BeierleSchobelVogeletal.2021,
  author    = {Beierle, Felix and Schobel, Johannes and Vogel, Carsten and Allgaier, Johannes and Mulansky, Lena and Haug, Fabian and Haug, Julian and Schlee, Winfried and Holfelder, Marc and Stach, Michael and Schickler, Marc and Baumeister, Harald and Cohrdes, Caroline and Deckert, J{\"u}rgen and Deserno, Lorenz and Edler, Johanna-Sophie and Eichner, Felizitas A. and Greger, Helmut and Hein, Grit and Heuschmann, Peter and John, Dennis and Kestler, Hans A. and Krefting, Dagmar and Langguth, Berthold and Meybohm, Patrick and Probst, Thomas and Reichert, Manfred and Romanos, Marcel and St{\"o}rk, Stefan and Terhorst, Yannik and Weiß, Martin and Pryss, R{\"u}diger},
  title     = {Corona Health — A Study- and Sensor-Based Mobile App Platform Exploring Aspects of the COVID-19 Pandemic},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {18},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {14},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph18147395},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242658},
  year      = {2021},
  abstract  = {Physical and mental well-being during the COVID-19 pandemic is typically assessed via surveys, which might make it difficult to conduct longitudinal studies and might lead to data suffering from recall bias. Ecological momentary assessment (EMA) driven smartphone apps can help alleviate such issues, allowing for in situ recordings. Implementing such an app is not trivial, necessitates strict regulatory and legal requirements, and requires short development cycles to appropriately react to abrupt changes in the pandemic. Based on an existing app framework, we developed Corona Health, an app that serves as a platform for deploying questionnaire-based studies in combination with recordings of mobile sensors. In this paper, we present the technical details of Corona Health and provide first insights into the collected data. Through collaborative efforts from experts from public health, medicine, psychology, and computer science, we released Corona Health publicly on Google Play and the Apple App Store (in July 2020) in eight languages and attracted 7290 installations so far. Currently, five studies related to physical and mental well-being are deployed and 17,241 questionnaires have been filled out. Corona Health proves to be a viable tool for conducting research related to the COVID-19 pandemic and can serve as a blueprint for future EMA-based studies. The data we collected will substantially improve our knowledge on mental and physical health states, traits and trajectories as well as its risk and protective factors over the course of the COVID-19 pandemic and its diverse prevention measures.},
  language  = {en}
}
@article{LotzHerrmannNotzetal.2021,
  author    = {Lotz, Christopher and Herrmann, Johannes and Notz, Quirin and Meybohm, Patrick and Kehl, Franz},
  title     = {Mitochondria and pharmacologic cardiac conditioning — At the heart of ischemic injury},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {6},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22063224},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285368},
  year      = {2021},
  abstract  = {Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.},
  language  = {en}
}
@article{TelesYanoVillarinhoetal.2021,
  author    = {Teles, Ramon Handerson Gomes and Yano, Rafael Sussumu and Villarinho, Nicolas Jones and Yamagata, Ana Sayuri and Jaeger, Ruy Gastaldoni and Meybohm, Patrick and Burek, Malgorzata and Freitas, Vanessa Morais},
  title     = {Advances in breast cancer management and extracellular vesicle research, a bibliometric analysis},
  series = {Current Oncology},
  volume    = {28},
  journal   = {Current Oncology},
  number    = {6},
  issn      = {1718-7729},
  doi       = {10.3390/curroncol28060382},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284321},
  pages     = {4504 -- 4520},
  year      = {2021},
  abstract  = {Extracellular vesicles transport variable content and have crucial functions in cell-cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, we aimed to investigate the trends in breast cancer management involved with extracellular vesicle research. Articles were retrieved from Scopus, including all the documents published concerning breast cancer and extracellular vesicles. We analyzed authors, journals, citations, affiliations, and keywords, besides other bibliometric analyses, using R Studio version 3.6.2. and VOSviewer version 1.6.0. A total of 1151 articles were retrieved, and as the main result, our analysis revealed trending topics on biomarkers of liquid biopsy, drug delivery, chemotherapy, autophagy, and microRNA. Additionally, research related to extracellular vesicles in breast cancer has been focused on diagnosis, treatment, and mechanisms of action of breast tumor-derived vesicles. Future studies are expected to explore the role of extracellular vesicles on autophagy and microRNA, besides investigating the application of extracellular vesicles from liquid biopsies for biomarkers and drug delivery, enabling the development and validation of therapeutic strategies for specific cancers.},
  language  = {en}
}
@article{SchmittMeybohmNeefetal.2022,
  author    = {Schmitt, Elke and Meybohm, Patrick and Neef, Vanessa and Baumgarten, Peter and Bayer, Alexandra and Choorapoikayil, Suma and Friederich, Patrick and Friedrich, Jens and Geisen, Christof and G{\"u}resir, Erdem and Gr{\"u}newald, Matthias and Gutjahr, Martin and Helmer, Philipp and Herrmann, Eva and M{\"u}ller, Markus and Narita, Diana and Raadts, Ansgar and Schwendner, Klaus and Seifried, Erhard and Stark, Patrick and Steinbicker, Andrea U. and Thoma, Josef and Velten, Markus and Weigt, Henry and Wiesenack, Christoph and Wittmann, Maria and Zacharowski, Kai and Piekarski, Florian},
  title     = {Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage - a multicentre subanalysis of the German PBM Network Registry},
  series = {Acta Neurochirurgica},
  volume    = {164},
  journal   = {Acta Neurochirurgica},
  organization    = {German PBM Network Collaborators},
  doi       = {10.1007/s00701-022-05144-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346754},
  pages     = {985-999},
  year      = {2022},
  abstract  = {Purpose Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. Methods This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. Results A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3\% in aSAH and 40.9\% in ICH. RBC transfusion rates were 29.9\% in aSAH and 29.3\% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications. Conclusions Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH.},
  language  = {en}
}
@article{KippnichKippnichErhardetal.2022,
  author    = {Kippnich, Maximilian and Kippnich, Uwe and Erhard, Harald and Meybohm, Patrick and Wurmb, Thomas},
  title     = {Weiterentwicklung im Katastrophenschutz: Ziel, Strategie und Taktik am Beispiel der Hochwasserkatastrophe 2021 im Ahrtal},
  series = {Notfall + Rettungsmedizin},
  journal   = {Notfall + Rettungsmedizin},
  issn      = {1434-6222},
  doi       = {10.1007/s10049-022-01089-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346737},
  pages     = {1-10},
  year      = {2022},
  abstract  = {Hintergrund und Fragestellung Im Rahmen der {\"u}ber{\"o}rtlichen Katastrophenhilfe war die Medizinische Task Force 47 (Unterfranken) im Juli 2021 bei der Hochwasserkatastrophe in Rheinland-Pfalz (Ahrtal) im Einsatz. Mit dem Ziel, m{\"o}gliche Verbesserungen im Katastrophenschutz aus Sicht einer {\"u}berregionalen Einheit aus dem Einsatz ableiten zu k{\"o}nnen, wurde dieser wissenschaftlich evaluiert und die Erkenntnisse in einen {\"u}bergeordneten Kontext gesetzt. Material und Methoden Nach Definition eines konkreten Auswerteprozesses wurden durch ein interdisziplin{\"a}res 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 Leistungsf{\"a}higkeit der Einsatzeinheiten k{\"o}nnte durch moderne Einsatzmittel (E-Bike, Drohnen, hochgel{\"a}ndeg{\"a}ngige Fahrzeuge) gesteigert werden. Zur Erh{\"o}hung der Reaktionsf{\"a}higkeit k{\"o}nnten neue Schnell-Einsatz-Gruppen (SEG) erforderlich sein, die als Teil von BOS-{\"u}bergreifenden Erkundungseinheiten agieren und in unwegsamen Gel{\"a}nden autark Einsatzauftr{\"a}ge abarbeiten k{\"o}nnen (SEG Erkundung und SEG Gel{\"a}nde-Infrastruktur-Logistik-Transport). Die taktischen Einheiten k{\"o}nnten in die regionale und {\"u}berregionale Katastrophenhilfe eingebunden und synchronisiert werden. Diskussion F{\"u}r den weitestgehend ehrenamtlich organisierten Katastrophenschutz in Deutschland k{\"o}nnte es in Zukunft erschwert sein, die Vielzahl m{\"o}glicher modernster Einsatzmittel im hochkomplexen Umfeld einer Katastrophe sicher einsetzen zu k{\"o}nnen. Eine Teilprofessionalisierung durch hauptamtliche F{\"u}hrungs- und Einsatzkr{\"a}fte k{\"o}nnte eine L{\"o}sung hierf{\"u}r sein.},
  language  = {de}
}
@article{KippnichSkazelKlingshirnetal.2022,
  author    = {Kippnich, Maximilian and Skazel, Tobias and Klingshirn, Hanna and Gerken, Laura and Heuschmann, Peter and Haas, Kirsten and Schutzmeier, Martha and Brandstetter, Lilly and Weismann, Dirk and Reuschenbach, Bernd and Meybohm, Patrick and Wurmb, Thomas},
  title     = {Analyse des Weaningprozesses bei Intensivpatienten im Hinblick auf Dokumentation und Verlegung in weiterbehandelnde Einheiten},
  series = {Medizinische Klinik, Intensivmedizin und Notfallmedizin},
  volume    = {118},
  journal   = {Medizinische Klinik, Intensivmedizin und Notfallmedizin},
  doi       = {10.1007/s00063-022-00941-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346742},
  pages     = {269-276},
  year      = {2022},
  abstract  = {Hintergrund und Fragestellung Die Entw{\"o}hnung von Beatmungsger{\"a}ten wird nicht immer auf der prim{\"a}r behandelnden Intensivstation abgeschlossen. Die Weiterverlegung in andere Behandlungseinrichtungen stellt einen sensiblen Abschnitt in der Behandlung und Rehabilitation des Weaningpatienten dar. Ziel der vorliegenden Studie war die Untersuchung des {\"U}berleitungsmanagements und des Interhospitaltransfers von Weaningpatienten unter besonderer Ber{\"u}cksichtigung der Dokumentationsqualit{\"a}t. Methodik Es erfolge eine retrospektive Datenanalyse eines Jahrs (2018) auf 2 Intensivstationen eines Universit{\"a}tsklinikums. Eingeschlossen wurden alle beatmeten Patienten mit folgenden Tracerdiagnosen: COPD, Asthma, Polytrauma, Pneumonie, Sepsis, ARDS und Reanimation (Beatmung > 24 h). Ergebnisse Insgesamt konnten 750 Patienten in die Untersuchung eingeschlossen werden (Alter 64 [52, 8-76; Median, IQR]; 32 \% weiblich). Davon waren 48 (6,4 \%) Patienten zum Zeitpunkt der Verlegung nicht entw{\"o}hnt (v. a. Sepsis und ARDS). Die Routinedokumentation war bei den Abschnitten „Spontaneous Breathing Trial", „Bewertung der Entw{\"o}hungsbereitschaft" und „vermutete Entw{\"o}hnbarkeit" ausreichend, um die Erf{\"u}llung der Parameter der S2k-Leitlinie „Prolongiertes Weaning" ad{\"a}quat zu beurteilen. Vorwiegend wurden diese Patienten mit Tracheostoma (76 \%) in Rehabilitationskliniken (44 \%) mittels spezialisierten Rettungsmitteln des arztbegleiteten Patiententransports verlegt (75 \%). Diskussion Die Verlegung nicht entw{\"o}hnter Patienten nach initialem Intensivaufenthalt ist ein relevantes Thema f{\"u}r den Interhospitaltransfer. Die Routinedokumentation eines strukturierten Weaningprozesses ist in Kernelementen ausreichend, um den Weaningprozess l{\"u}ckenlos zu beschreiben. Dies ist f{\"u}r die Kontinuit{\"a}t in der Weiterbehandlung dieser Patienten von großer Bedeutung.},
  language  = {de}
}
@article{NowackaChmielewskaGrabowskaGrabowskietal.2022,
  author    = {Nowacka-Chmielewska, Marta and Grabowska, Konstancja and Grabowski, Mateusz and Meybohm, Patrick and Burek, Malgorzata and Małecki, Andrzej},
  title     = {Running from stress: neurobiological mechanisms of exercise-induced stress resilience},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {21},
  issn      = {1422-0067},
  doi       = {10.3390/ijms232113348},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297407},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{FeldheimWendLaueretal.2022,
  author    = {Feldheim, Jonas and Wend, David and Lauer, Mara J. and Monoranu, Camelia M. and Glas, Martin and Kleinschnitz, Christoph and Ernestus, Ralf-Ingo and Braunger, Barbara M. and Meybohm, Patrick and Hagemann, Carsten and Burek, Malgorzata},
  title     = {Protocadherin Gamma C3 (PCDHGC3) is strongly expressed in glioblastoma and its high expression is associated with longer progression-free survival of patients},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {15},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23158101},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284433},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{HillDossowHeylandetal.2022,
  author    = {Hill, Aileen and Dossow, Vera von and Heyland, Daren K. and Rossaint, Rolf and Meybohm, Patrick and Fox, Henrik and Morshuis, Michiel and Elke, Gunnar and Panholzer, Bernd and Haneya, Assad and B{\"o}ning, Andreas and Niemann, Bernd and Zayat, Rashad and Moza, Ajay and Stoppe, Christian},
  title     = {Preoperative nutritional optimization and physical exercise for patients scheduled for elective implantation for a left-ventricular assist device — The PROPER-LVAD study},
  series = {Surgeries},
  volume    = {3},
  journal   = {Surgeries},
  number    = {4},
  issn      = {2673-4095},
  doi       = {10.3390/surgeries3040031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288317},
  pages     = {284 -- 296},
  year      = {2022},
  abstract  = {Background: Prehabilitation is gaining increasing interest and shows promising effects on short- and long-term outcomes among patients undergoing major surgery. The effect of multimodal, interdisciplinary prehabilitation has not yet been studied in patients with severe heart failure scheduled for the implantation of a left-ventricular assist device (LVAD). Methods: This randomized controlled multi-center study evaluates the effect of preoperative combined optimization of nutritional and functional status. Patients in the intervention group are prescribed daily in-bed cycling and oral nutrition supplements (ONS) from study inclusion until the day before LVAD-implantation. Patients in the control group receive standard of care treatment. The primary outcomes for the pilot study that involves 48 patients are safety (occurrence of adverse events), efficacy (group separation regarding the intake of macronutrients), feasibility of the trial protocol (compliance (percentage of received interventions) and confirmation of recruitment rates. Secondary outcomes include longitudinal measurements of muscle mass, muscle strength, physical function and quality of life, next to traditional clinical outcomes (30-day mortality, hospital and ICU length of stay, duration of mechanical ventilation and number of complications and infections). If the pilot study is successful, a larger confirmatory, international multicenter study is warranted.},
  language  = {en}
}
@article{HelmerHelfSammethetal.2022,
  author    = {Helmer, Philipp and Helf, Daniel and Sammeth, Michael and Winkler, Bernd and Hottenrott, Sebastian and Meybohm, Patrick and Kranke, Peter},
  title     = {The use of non-invasive continuous blood pressure measuring (ClearSight\(^®\)) during central neuraxial anaesthesia for caesarean section — a retrospective validation study},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {15},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11154498},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286042},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{FiedlerMuellenbachRolfesetal.2022,
  author    = {Fiedler, Mascha O. and Muellenbach, Ralf M. and Rolfes, Caroline and Lotz, Christopher and Nickel, Felix and M{\"u}ller-Stich, Beat P. and Supady, Alexander and Lepper, Philipp M. and Weigand, Markus A. and Meybohm, Patrick and Kalenka, Armin and Reyher, Christian},
  title     = {Pumpless extracorporeal hemadsorption technique (pEHAT): a proof-of-concept animal study},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {22},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11226815},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297347},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{HelmerHottenrottSteinischetal.2022,
  author    = {Helmer, Philipp and Hottenrott, Sebastian and Steinisch, Andreas and R{\"o}der, Daniel and Schubert, J{\"o}rg and Steigerwald, Udo and Choorapoikayil, Suma and Meybohm, Patrick},
  title     = {Avoidable blood loss in critical care and patient blood management: scoping review of diagnostic blood loss},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {2},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11020320},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255145},
  year      = {2022},
  abstract  = {Background: Anemia remains one of the most common comorbidities in intensive care patients worldwide. The cause of anemia is often multifactorial and triggered by underlying disease, comorbidities, and iatrogenic factors, such as diagnostic phlebotomies. As anemia is associated with a worse outcome, especially in intensive care patients, unnecessary iatrogenic blood loss must be avoided. Therefore, this scoping review addresses the amount of blood loss during routine phlebotomies in adult (>17 years) intensive care patients and whether there are factors that need to be improved in terms of patient blood management (PBM). Methods: A systematic search of the Medline Database via PubMed was conducted according to PRISMA guidelines. The reported daily blood volume for diagnostics and other relevant information from eligible studies were charted. Results: A total of 2167 studies were identified in our search, of which 38 studies met the inclusion criteria (9 interventional studies and 29 observational studies). The majority of the studies were conducted in the US (37\%) and Canada (13\%). An increasing interest to reduce iatrogenic blood loss has been observed since 2015. Phlebotomized blood volume per patient per day was up to 377 mL. All interventional trials showed that the use of pediatric-sized blood collection tubes can significantly reduce the daily amount of blood drawn. Conclusion: Iatrogenic blood loss for diagnostic purposes contributes significantly to the development and exacerbation of hospital-acquired anemia. Therefore, a comprehensive PBM in intensive care is urgently needed to reduce avoidable blood loss, including blood-sparing techniques, regular advanced training, and small-volume blood collection tubes.},
  language  = {en}
}
@article{SitterSchlesingerReinholdetal.2022,
  author    = {Sitter, Magdalena and Schlesinger, Tobias and Reinhold, Ann-Kristin and Scholler, Axel and Heymann, Christian von and Welfle, Sabine and Bartmann, Catharina and W{\"o}ckel, Achim and Kleinschmidt, Stefan and Schneider, Sven and Gottschalk, Andr{\´e} and Greve, Susanne and Wermelt, Julius Z. and Wiener, Roland and Schulz, Frank and Chappell, Daniel and Brunner, Maya and Neumann, Claudia and Meybohm, Patrick and Kranke, Peter},
  title     = {COVID-19 in der geburtshilflichen An{\"a}sthesie: Prospektive Erfassung von SARS-CoV-2-Infektionen zum Zeitpunkt der Geburt sowie des peripartalen Verlaufs SARS-CoV-2-positiver Schwangerer},
  series = {Der Anaesthesist},
  volume    = {71},
  journal   = {Der Anaesthesist},
  number    = {6},
  issn      = {1432-055X},
  doi       = {10.1007/s00101-021-01068-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264878},
  pages     = {452-461},
  year      = {2022},
  abstract  = {Hintergrund Im Rahmen der Pandemie des SARS-CoV-2-Virus erlangte das Patientenkollektiv der Schwangeren fr{\"u}h Aufmerksamkeit. Initial wurde angesichts sich fr{\"u}h abzeichnender Krankheitsf{\"a}lle bei j{\"u}ngeren Patienten mit einem erheblichen Aufkommen peripartal zu betreuender, COVID-19-positiver Schwangerer gerechnet. Ziel der Arbeit Diese Arbeit vermittelt einen Einblick in die SARS-CoV-2-Infektionszahlen im Rahmen der geburtshilflichen An{\"a}sthesie zu Beginn der Pandemie sowie w{\"a}hrend der zweiten Infektionswelle in Deutschland. Methoden {\"U}ber das COALA-Register (COVID-19 related Obstetric Anaesthesia Longitudinal Assessment-Registry) wurden sowohl von M{\"a}rz bis Mai 2020 als auch von Oktober 2020 bis Februar 2021 in Deutschland und der Schweiz w{\"o}chentlich prospektiv Daten zu Verdachts- und best{\"a}tigten SARS-CoV-2-F{\"a}llen bei Schwangeren zum Zeitpunkt der Geburt erhoben. Betrachtet wurden die Verteilung dieser auf die Anzahl der Geburten, Zentren und Erhebungswochen sowie m{\"u}tterliche Charakteristika und Krankheitsverl{\"a}ufe. Ergebnisse Neun Zentren haben im Verlauf 44 SARS-CoV-2-positive Schwangere zum Zeitpunkt der Geburt bei 7167 Geburten (0,6 \%) gemeldet (3 F{\"a}lle auf 2270 Geburten (0,4 \%) und 41 F{\"a}lle auf 4897 Geburten (0,8 \%)). Berichtet wurden 2 schwere COVID-19-Verl{\"a}ufe (n = 1 mit Todesfolge nach ECMO, n = 1 mit ECMO {\"u}berlebt). Bei 28 (68 \%) Patientinnen verlief die Infektion asymptomatisch. Ein Neugeborenes wurde im Verlauf positiv auf SARS-CoV‑2 getestet. Schlussfolgerung Mithilfe des Registers konnte das Auftreten von F{\"a}llen zu Beginn der Pandemie zeitnah eingesch{\"a}tzt werden. Es traten sporadisch Verdachtsf{\"a}lle bzw. best{\"a}tigte F{\"a}lle auf. Aufgrund fehlender fl{\"a}chendeckender Testung muss aber von einer Dunkelziffer asymptomatischer F{\"a}lle ausgegangen werden. W{\"a}hrend der zweiten Infektionswelle wurden 68 \% asymptomatische F{\"a}lle gemeldet. Jedoch kann es bei jungen, gesunden Patientinnen ohne das Vorliegen typischer Risikofaktoren zu schwerwiegenden Verl{\"a}ufen kommen.},
  language  = {de}
}
@article{SitterPecksRuedigeretal.2022,
  author    = {Sitter, Magdalena and Pecks, Ulrich and R{\"u}diger, Mario and Friedrich, Sabine and Fill Malfertheiner, Sara and Hein, Alexander and K{\"o}nigbauer, Josefine T. and Becke-Jakob, Karin and Z{\"o}llkau, Janine and Ramsauer, Babett and Rathberger, Katharina and Pontones, Constanza A. and Kraft, Katrina and Meybohm, Patrick and H{\"a}rtel, Christoph and Kranke, Peter},
  title     = {Pregnant and postpartum women requiring intensive care treatment for COVID-19 — first data from the CRONOS-registry},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {3},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11030701},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255257},
  year      = {2022},
  abstract  = {(1) Background: Data on coronavirus 2 infection during pregnancy vary. We aimed to describe maternal characteristics and clinical presentation of SARS-CoV-2 positive women requiring intensive care treatment for COVID-19 during pregnancy and postpartum period based on data of a comprehensive German surveillance system in obstetric patients. (2) Methods: Data from COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS), a prospective multicenter registry for SARS-CoV-2 positive pregnant women, was analyzed with respect to ICU treatment. All women requiring intensive care treatment for COVID-19 were included and compared regarding maternal characteristics, course of disease, as well as maternal and neonatal outcomes. (3) Results: Of 2650 cases in CRONOS, 101 women (4\%) had a documented ICU stay. Median maternal age was 33 (IQR, 30-36) years. COVID-19 was diagnosed at a median gestational age of 33 (IQR, 28-35) weeks. As the most invasive form of COVID-19 treatment interventions, patients received either continuous monitoring of vital signs without further treatment requirement (n = 6), insufflation of oxygen (n = 30), non-invasive ventilation (n = 22), invasive ventilation (n = 28), or escalation to extracorporeal membrane oxygenation (n = 15). No significant clinical differences were identified between patients receiving different forms of ventilatory support for COVID-19. Prevalence of preterm delivery was significantly higher in women receiving invasive respiratory treatments. Four women died of COVID-19 and six fetuses were stillborn. (4) Conclusions: Our cohort shows that progression of COVID-19 is rare in pregnant and postpartum women treated in the ICU. Preterm birth rate is high and COVID-19 requiring respiratory support increases the risk of poor maternal and neonatal outcome.},
  language  = {en}
}
@article{FischerThiesAwadetal.2022,
  author    = {Fischer, Dania and Thies, Fabian and Awad, Omar and Brat, Camilla and Meybohm, Patrick and Baer, Patrick C. and M{\"u}ller, Markus M. and Urbschat, Anja and Maier, Thorsten J. and Zacharowski, Kai and Roos, Jessica},
  title     = {Red blood cell-derived microparticles exert no cancer promoting effects on colorectal cancer cells in vitro},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {16},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23169323},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286018},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{MengerLeeNotzetal.2022,
  author    = {Menger, Johannes and Lee, Zheng-Yii and Notz, Quirin and Wallqvist, Julia and Hasan, M. Shahnaz and Elke, Gunnar and Dworschak, Martin and Meybohm, Patrick and Heyland, Daren K. and Stoppe, Christian},
  title     = {Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials},
  series = {Critical Care},
  volume    = {26},
  journal   = {Critical Care},
  number    = {1},
  doi       = {10.1186/s13054-022-04139-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299700},
  year      = {2022},
  abstract  = {Background The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration. Methods Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials. Results Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95\% confidence interval 0.62-0.97, p = 0.03; I2 = 30\%), reduced intensive care unit length of stay (12 studies: mean difference - 3.13 days, 95\% CI - 5.36 to - 0.89, n = 1250, p = 0.006; I2 = 70\%), and shorter duration of mechanical ventilation (9 studies: mean difference - 5.07 days, 95\% CI - 7.42 to - 2.73, n = 572, p < 0.0001; I2 = 54\%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels. Conclusions Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results.},
  language  = {en}
}
@article{CurtazReifschlaegerStraehleetal.2022,
  author    = {Curtaz, Carolin J. and Reifschl{\"a}ger, Leonie and Str{\"a}hle, Linus and Feldheim, Jonas and Feldheim, Julia J. and Schmitt, Constanze and Kiesel, Matthias and Herbert, Saskia-Laureen and W{\"o}ckel, Achim and Meybohm, Patrick and Burek, Malgorzata},
  title     = {Analysis of microRNAs in exosomes of breast cancer patients in search of molecular prognostic factors in brain metastases},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {7},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23073683},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284476},
  year      = {2022},
  abstract  = {Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.},
  language  = {en}
}
@article{HerrmannLotzKaragiannidisetal.2022,
  author    = {Herrmann, Johannes and Lotz, Christopher and Karagiannidis, Christian and Weber-Carstens, Steffen and Kluge, Stefan and Putensen, Christian and Wehrfritz, Andreas and Schmidt, Karsten and Ellerkmann, Richard K. and Oswald, Daniel and Lotz, G{\"o}sta and Zotzmann, Viviane and Moerer, Onnen and K{\"u}hn, Christian and Kochanek, Matthias and Muellenbach, Ralf and Gaertner, Matthias and Fichtner, Falk and Brettner, Florian and Findeisen, Michael and Heim, Markus and Lahmer, Tobias and Rosenow, Felix and Haake, Nils and Lepper, Philipp M. and Rosenberger, Peter and Braune, Stephan and Kohls, Mirjam and Heuschmann, Peter and Meybohm, Patrick},
  title     = {Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation},
  series = {Critical Care},
  volume    = {26},
  journal   = {Critical Care},
  number    = {1},
  doi       = {10.1186/s13054-022-04053-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299686},
  year      = {2022},
  abstract  = {Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO\(_{2}\)/FiO\(_{2}\) ratio prior to ECMO was 72 mmHg (IQR: 58-99). ICU survival was 31.4\%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42\%) patients fulfilling modified EOLIA criteria had a higher survival (38\%) (p = 0.0014, OR 0.64 (CI 0.41-0.99)). Survival differed between low, intermediate, and high-volume centers with 20\%, 30\%, and 38\%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28-1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival.},
  language  = {en}
}
@article{NotzLeeMengeretal.2022,
  author    = {Notz, Quirin and Lee, Zheng-Yii and Menger, Johannes and Elke, Gunnar and Hill, Aileen and Kranke, Peter and Roeder, Daniel and Lotz, Christopher and Meybohm, Patrick and Heyland, Daren K. and Stoppe, Christian},
  title     = {Omega-6 sparing effects of parenteral lipid emulsions-an updated systematic review and meta-analysis on clinical outcomes in critically ill patients},
  series = {Critical Care},
  volume    = {26},
  journal   = {Critical Care},
  number    = {1},
  doi       = {10.1186/s13054-022-03896-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299710},
  year      = {2022},
  abstract  = {Background Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients. Methods A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed. Results 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95\% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95\% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] - 6.88; 95\% CI - 11.27, - 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD - 3.53; 95\% CI - 6.16, - 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95\% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care. Conclusion Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact.},
  language  = {en}
}
@article{CurtazKieselMeybohmetal.2022,
  author    = {Curtaz, Carolin J. and Kiesel, Ludwig and Meybohm, Patrick and W{\"o}ckel, Achim and Burek, Malgorzata},
  title     = {Anti-hormonal therapy in breast cancer and its effect on the blood-brain barrier},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {20},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14205132},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290320},
  year      = {2022},
  abstract  = {Simple Summary Anti-hormonal therapie regimes are well established in oncological treatments in breast cancer. In contrast there is limited knowledge of their effects on metastatic brain metastases in advanced breast cancer and their ability to cross the blood brain-barrier. In this review, we point out the usual antihormonal therapy options in the primary disease, but also in metastatic breast cancer. In addition, we explain the epidemiological facts of brain metastases, as well as the basics of the blood-brain barrier and how this is overcome by metastase. Last but not least, we deal with the known anti-hormonal therapy options and present clinical studies on their intracerebral effect, as well as the known basics of their blood-brain barrier penetration. Not all common anti-hormonal therapeutics are able to penetrate the CNS. It is therefore important for the treating oncologists to use substances that have been proven to cross the BBB, despite the limited data available. Aromataseinhibitors, especially letrozole, probably also tamoxifen, everolimus and CDK4/6 inhibitors, especially abemaciclib, appear to act intracerebrally by overcoming the blood-brain barrier. Nevertheless, further data must be obtained in basic research, but also health care research in relation to patients with brain metastases. Abstract The molecular receptor status of breast cancer has implications for prognosis and long-term metastasis. Although metastatic luminal B-like, hormone-receptor-positive, HER2-negative, breast cancer causes brain metastases less frequently than other subtypes, though tumor metastases in the brain are increasingly being detected of this patient group. Despite the many years of tried and tested use of a wide variety of anti-hormonal therapeutic agents, there is insufficient data on their intracerebral effectiveness and their ability to cross the blood-brain barrier. In this review, we therefore summarize the current state of knowledge on anti-hormonal therapy and its intracerebral impact and effects on the blood-brain barrier in breast cancer.},
  language  = {en}
}
@article{SunBlecharzLangMałeckietal.2022,
  author    = {Sun, Aili and Blecharz-Lang, Kinga G. and Małecki, Andrzej and Meybohm, Patrick and Nowacka-Chmielewska, Marta M. and Burek, Malgorzata},
  title     = {Role of microRNAs in the regulation of blood-brain barrier function in ischemic stroke and under hypoxic conditions in vitro},
  series = {Frontiers in Drug Delivery},
  volume    = {2},
  journal   = {Frontiers in Drug Delivery},
  issn      = {2674-0850},
  doi       = {10.3389/fddev.2022.1027098},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-291423},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{HelmerHottenrottRodemersetal.2022,
  author    = {Helmer, Philipp and Hottenrott, Sebastian and Rodemers, Philipp and Leppich, Robert and Helwich, Maja and Pryss, R{\"u}diger and Kranke, Peter and Meybohm, Patrick and Winkler, Bernd E. and Sammeth, Michael},
  title     = {Accuracy and Systematic Biases of Heart Rate Measurements by Consumer-Grade Fitness Trackers in Postoperative Patients: Prospective Clinical Trial},
  series = {Journal of Medical Internet Research},
  volume    = {24},
  journal   = {Journal of Medical Internet Research},
  number    = {12},
  doi       = {10.2196/42359},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299679},
  year      = {2022},
  abstract  = {Background: Over the recent years, technological advances of wrist-worn fitness trackers heralded a new era in the continuous monitoring of vital signs. So far, these devices have primarily been used for sports. Objective: However, for using these technologies in health care, further validations of the measurement accuracy in hospitalized patients are essential but lacking to date. Methods: We conducted a prospective validation study with 201 patients after moderate to major surgery in a controlled setting to benchmark the accuracy of heart rate measurements in 4 consumer-grade fitness trackers (Apple Watch 7, Garmin Fenix 6 Pro, Withings ScanWatch, and Fitbit Sense) against the clinical gold standard (electrocardiography). Results: All devices exhibited high correlation (r≥0.95; P<.001) and concordance (rc≥0.94) coefficients, with a relative error as low as mean absolute percentage error <5\% based on 1630 valid measurements. We identified confounders significantly biasing the measurement accuracy, although not at clinically relevant levels (mean absolute error<5 beats per minute). Conclusions: Consumer-grade fitness trackers appear promising in hospitalized patients for monitoring heart rate.},
  language  = {en}
}
@article{LindhoffLastBirschmannBidenharnetal.2022,
  author    = {Lindhoff-Last, Edelgard and Birschmann, Ingvild and Bidenharn, Antonia J. and Kuhn, Joachim and Lindau, Simone and Konstantinides, Stavros and Grottke, Oliver and Nowak-G{\"o}ttl, Ulrike and Lucks, Jessica and Zydek, Barbara and Heymann, Christian von and S{\"u}mnig, Ariane and Beyer-Westendorf, Jan and Schellong, Sebastian and Meybohm, Patrick and Greinacher, Andreas and Herrmann, Eva},
  title     = {Pharmacokinetics of phenprocoumon in emergency situations - results of the prospective observational RADOA-registry (reversal agent use in patients treated with direct oral anticoagulants or vitamin K antagonists registry)},
  series = {Pharmaceuticals},
  volume    = {15},
  journal   = {Pharmaceuticals},
  number    = {11},
  issn      = {1424-8247},
  doi       = {10.3390/ph15111437},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297226},
  year      = {2022},
  abstract  = {Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6\% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22\% vs. 4.2\% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days.},
  language  = {en}
}
@article{HackenbroichKrankeMeybohmetal.2022,
  author    = {Hackenbroich, Samantha and Kranke, Peter and Meybohm, Patrick and Weibel, Stephanie},
  title     = {Include or not to include conference abstracts in systematic reviews? Lessons learned from a large Cochrane network meta-analysis including 585 trials},
  series = {Systematic Reviews},
  volume    = {11},
  journal   = {Systematic Reviews},
  number    = {1},
  doi       = {10.1186/s13643-022-02048-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299660},
  year      = {2022},
  abstract  = {Background Systematic reviews attempt to gather all available evidence. Controversy exists regarding effort and benefit of including study results presented at conferences only. We recently published a Cochrane network meta-analysis (NMA) including 585 randomized controlled trials comparing drugs for prevention of postoperative nausea and vomiting (PONV). Studies published as conference abstracts only were excluded. This study aimed to include all eligible studies published as abstracts only, assessing their added value regarding reporting quality and effect on the review's interpretation. Methods Conference abstracts were searched in the review's excluded studies and conference proceedings of anaesthesiologic societies. We assessed their reporting quality regarding review's eligibility criteria, Cochrane 'risk of bias' assessment tool 1.0, and adherence to CONSORT (Consolidated Standards of Reporting Trials) for abstracts. Abstracts were included in sensitivity NMA, and impact on the NMA structure was investigated. Results We identified 90 abstracts. A total of 14\% (13/90) were eligible. A total of 86\% (77/90) are awaiting classification due to insufficient reporting of review's eligibility criteria. In abstracts awaiting classification, sufficient information was missing on standardization of anaesthesia in 71\% (55/77), age of participants in 56\% (43/77), and outcome details in 46\% (36/77). A total of 73\% (66/90) of abstracts lacked sufficient information on 15/25 data extraction items. Reported study characteristics of abstracts were comparable to included studies of the review. A total of 62\% (56/90) of abstract trials were assessed as overall high risk of bias due to poor reporting. Median adherence to CONSORT for abstracts was 24\% (IQR, 18 to 29\%). Six of the 13 eligible abstracts reported relevant outcome data in sufficient detail for NMA on seven outcomes of the Cochrane review. Inclusion of abstracts did not substantially change the network structure, network effect estimates, ranking of treatments, or the conclusion. Certainty of evidence for headache on palonosetron use was upgraded from very low to low. Conclusions Most conference abstracts on PONV were insufficiently reported regarding review's narrow inclusion criteria and could not be included in NMA. The resource-intensive search and evaluation of abstracts did not substantially extent the full-text evidence base of the review, given the few adequately reported abstracts. Conferences should oblige authors to adhere to CONSORT for abstracts.},
  language  = {en}
}
@article{KippnichDuempertSchorscheretal.2022,
  author    = {Kippnich, Maximilian and Duempert, Maximilian and Schorscher, Nora and Jordan, Martin C. and Kunz, Andreas S. and Meybohm, Patrick and Wurmb, Thomas},
  title     = {Simultaneous treatment of trauma patients in a dual room trauma suite with integrated movable sliding gantry CT system: an observational study},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-022-20491-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299695},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{SchorscherKippnichMeybohmetal.2022,
  author    = {Schorscher, Nora and Kippnich, Maximilian and Meybohm, Patrick and Wurmb, Thomas},
  title     = {Lessons learned from terror attacks: thematic priorities and development since 2001 - results from a systematic review},
  series = {European Journal of Trauma and Emergency Surgery},
  volume    = {48},
  journal   = {European Journal of Trauma and Emergency Surgery},
  issn      = {1863-9941},
  doi       = {10.1007/s00068-021-01858-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264862},
  pages     = {2613-2638},
  year      = {2022},
  abstract  = {PURPOSE The threat of national and international terrorism remains high. Preparation is the key requirement for the resilience of hospitals and out-of-hospital rescue forces. The scientific evidence for defining medical and tactical strategies often feeds on the analysis of real incidents and the lessons learned derived from them. This systematic review of the literature aims to identify and systematically report lessons learned from terrorist attacks since 2001. METHODS PubMed was used as a database using predefined search strategies and eligibility criteria. All countries that are part of the Organization for Economic Cooperation and Development (OECD) were included. The time frame was set between 2001 and 2018. RESULTS Finally 68 articles were included in the review. From these, 616 lessons learned were extracted and summarized into 15 categories. The data shows that despite the difference in attacks, countries, and casualties involved, many of the lessons learned are similar. We also found that the pattern of lessons learned is repeated continuously over the time period studied. CONCLUSIONS The lessons from terrorist attacks since 2001 follow a certain pattern and remained constant over time. Therefore, it seems to be more accurate to talk about lessons identified rather than lessons learned. To save as many victims as possible, protect rescue forces from harm, and to prepare hospitals at the best possible level it is important to implement the lessons identified in training and preparation.},
  language  = {en}
}
@article{LambertiniHartrampfHiguchietal.2022,
  author    = {Lambertini, Alessandro and Hartrampf, Philipp E. and Higuchi, Takahiro and Serfling, Sebastian E. and Meybohm, Patrick and Schirbel, Andreas and Buck, Andreas K. and Werner, Rudolf A.},
  title     = {CXCR4-targeted molecular imaging after severe SARS-Cov-2 infection},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {50},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {1},
  doi       = {10.1007/s00259-022-05932-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324619},
  pages     = {228-229},
  year      = {2022},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{SitterFroehlichKrankeetal.2023,
  author    = {Sitter, Magdalena and Fr{\"o}hlich, Corinna and Kranke, Peter and Markus, Christian and W{\"o}ckel, Achim and Rehn, Monika and Bartmann, Catharina and Frieauff, Eric and Meybohm, Patrick and Pecks, Ulrich and R{\"o}der, Daniel},
  title     = {ECMO-Therapie bei COVID-19-ARDS in der Schwangerschaft erm{\"o}glicht den Erhalt einer Schwangerschaft mit termingerechter Entbindung},
  series = {Die Anaesthesiologie},
  volume    = {72},
  journal   = {Die Anaesthesiologie},
  number    = {3},
  doi       = {10.1007/s00101-022-01232-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346762},
  pages     = {166-170},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {de}
}
@article{HenckertMalorgioSchweigeretal.2023,
  author    = {Henckert, David and Malorgio, Amos and Schweiger, Giovanna and Raimann, Florian J. and Piekarski, Florian and Zacharowski, Kai and Hottenrott, Sebastian and Meybohm, Patrick and Tscholl, David W. and Spahn, Donat R. and Roche, Tadzio R.},
  title     = {Attitudes of anesthesiologists toward artificial intelligence in anesthesia: a multicenter, mixed qualitative-quantitative study},
  series = {Journal of Clinical Medicine},
  volume    = {12},
  journal   = {Journal of Clinical Medicine},
  number    = {6},
  issn      = {2077-0383},
  doi       = {10.3390/jcm12062096},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311189},
  year      = {2023},
  abstract  = {Artificial intelligence (AI) is predicted to play an increasingly important role in perioperative medicine in the very near future. However, little is known about what anesthesiologists know and think about AI in this context. This is important because the successful introduction of new technologies depends on the understanding and cooperation of end users. We sought to investigate how much anesthesiologists know about AI and what they think about the introduction of AI-based technologies into the clinical setting. In order to better understand what anesthesiologists think of AI, we recruited 21 anesthesiologists from 2 university hospitals for face-to-face structured interviews. The interview transcripts were subdivided sentence-by-sentence into discrete statements, and statements were then grouped into key themes. Subsequently, a survey of closed questions based on these themes was sent to 70 anesthesiologists from 3 university hospitals for rating. In the interviews, the base level of knowledge of AI was good at 86 of 90 statements (96\%), although awareness of the potential applications of AI in anesthesia was poor at only 7 of 42 statements (17\%). Regarding the implementation of AI in anesthesia, statements were split roughly evenly between pros (46 of 105, 44\%) and cons (59 of 105, 56\%). Interviewees considered that AI could usefully be used in diverse tasks such as risk stratification, the prediction of vital sign changes, or as a treatment guide. The validity of these themes was probed in a follow-up survey of 70 anesthesiologists with a response rate of 70\%, which confirmed an overall positive view of AI in this group. Anesthesiologists hold a range of opinions, both positive and negative, regarding the application of AI in their field of work. Survey-based studies do not always uncover the full breadth of nuance of opinion amongst clinicians. Engagement with specific concerns, both technical and ethical, will prove important as this technology moves from research to the clinic.},
  language  = {en}
}
@article{SchweigerMalorgioHenckertetal.2023,
  author    = {Schweiger, Giovanna and Malorgio, Amos and Henckert, David and Braun, Julia and Meybohm, Patrick and Hottenrott, Sebastian and Froehlich, Corinna and Zacharowski, Kai and Raimann, Florian J. and Piekarski, Florian and Noethiger, Christoph B. and Spahn, Donat R. and Tscholl, David W. and Roche, Tadzio R.},
  title     = {Visual Blood, a 3D animated computer model to optimize the interpretation of blood gas analysis},
  series = {Bioengineering},
  volume    = {10},
  journal   = {Bioengineering},
  number    = {3},
  issn      = {2306-5354},
  doi       = {10.3390/bioengineering10030293},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304150},
  year      = {2023},
  abstract  = {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.},
  language  = {en}
}
@article{BergauerAkbasBraunetal.2023,
  author    = {Bergauer, Lisa and Akbas, Samira and Braun, Julia and Ganter, Michael T. and Meybohm, Patrick and Hottenrott, Sebastian and Zacharowski, Kai and Raimann, Florian J. and Rivas, Eva and L{\´o}pez-Baamonde, Manuel and Spahn, Donat R. and Noethiger, Christoph B. and Tscholl, David W. and Roche, Tadzio R.},
  title     = {Visual Blood, visualisation of blood gas analysis in virtual reality, leads to more correct diagnoses: a computer-based, multicentre, simulation study},
  series = {Bioengineering},
  volume    = {10},
  journal   = {Bioengineering},
  number    = {3},
  issn      = {2306-5354},
  doi       = {10.3390/bioengineering10030340},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-310979},
  year      = {2023},
  abstract  = {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.},
  language  = {en}
}
@article{HerrmannMuellerNotzetal.2023,
  author    = {Herrmann, Johannes and M{\"u}ller, Kerstin and Notz, Quirin and H{\"u}bsch, Martha and Haas, Kirsten and Horn, Anna and Schmidt, Julia and Heuschmann, Peter and Maschmann, Jens and Frosch, Matthias and Deckert, J{\"u}rgen and Einsele, Hermann and Ertl, Georg and Frantz, Stefan and Meybohm, Patrick and Lotz, Christopher},
  title     = {Prospective single-center study of health-related quality of life after COVID-19 in ICU and non-ICU patients},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-33783-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357174},
  year      = {2023},
  abstract  = {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.},
  language  = {en}
}
@article{HelmerRodemersHottenrottetal.2023,
  author    = {Helmer, Philipp and Rodemers, Philipp and Hottenrott, Sebastian and Leppich, Robert and Helwich, Maja and Pryss, R{\"u}diger and Kranke, Peter and Meybohm, Patrick and Winkler, Bernd E. and Sammeth, Michael},
  title     = {Evaluating blood oxygen saturation measurements by popular fitness trackers in postoperative patients: a prospective clinical trial},
  series = {iScience},
  volume    = {26},
  journal   = {iScience},
  number    = {11},
  issn      = {2589-0042},
  doi       = {10.1016/j.isci.2023.108155},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349913},
  year      = {2023},
  abstract  = {Summary Blood oxygen saturation is an important clinical parameter, especially in postoperative hospitalized patients, monitored in clinical practice by arterial blood gas (ABG) and/or pulse oximetry that both are not suitable for a long-term continuous monitoring of patients during the entire hospital stay, or beyond. Technological advances developed recently for consumer-grade fitness trackers could—at least in theory—help to fill in this gap, but benchmarks on the applicability and accuracy of these technologies in hospitalized patients are currently lacking. We therefore conducted at the postanaesthesia care unit under controlled settings a prospective clinical trial with 201 patients, comparing in total >1,000 oxygen blood saturation measurements by fitness trackers of three brands with the ABG gold standard and with pulse oximetry. Our results suggest that, despite of an overall still tolerable measuring accuracy, comparatively high dropout rates severely limit the possibilities of employing fitness trackers, particularly during the immediate postoperative period of hospitalized patients. Highlights •The accuracy of O2 measurements by fitness trackers is tolerable (RMSE ≲4\%) •Correlation with arterial blood gas measurements is fair to moderate (PCC = [0.46; 0.64]) •Dropout rates of fitness trackers during O2 monitoring are high (∼1/3 values missing) •Fitness trackers cannot be recommended for O2 measuring during critical monitoring},
  language  = {en}
}
@article{SchmidEckertMeixneretal.2023,
  author    = {Schmid, Benedikt and Eckert, Dominik and Meixner, Andreas and Pistner, Paul and Malzahn, Uwe and Berberich, Monika and Happel, Oliver and Meybohm, Patrick and Kranke, Peter},
  title     = {Conventional versus video-assisted laryngoscopy for perioperative endotracheal intubation (COVALENT) - a randomized, controlled multicenter trial},
  series = {BMC Anesthesiology},
  volume    = {23},
  journal   = {BMC Anesthesiology},
  doi       = {10.1186/s12871-023-02083-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357207},
  year      = {2023},
  abstract  = {Background Data on the routine use of video-assisted laryngoscopy in peri-operative intubations are rather inconsistent and ambiguous, in part due to small populations and non-uniform outcome measures in past trials. Failed or prolonged intubation procedures are a reason for relevant morbidity and mortality. This study aims to determine whether video-assisted laryngoscopy (with both Macintosh-shaped and hyperangulated blades) is at least equal to the standard method of direct laryngoscopy with respect to the first-pass success rate. Furthermore, validated tools from the field of human factors will be applied to examine within-team communication and task load during this critical medical procedure. Methods In this randomized, controlled, three-armed parallel group design, multi-centre trial, a total of more than 2500 adult patients scheduled for perioperative endotracheal intubation will be randomized. In equally large arms, video-assisted laryngoscopy with a Macintosh-shaped or a hyperangulated blade will be compared to the standard of care (direct laryngoscopy with Macintosh blade). In a pre-defined hierarchical analysis, we will test the primary outcome for non-inferiority first. If this goal should be met, the design and projected statistical power also allow for subsequent testing for superiority of one of the interventions. Various secondary outcomes will account for patient safety considerations as well as human factors interactions within the provider team and will allow for further exploratory data analysis and hypothesis generation. Discussion This randomized controlled trial will provide a solid base of data in a field where reliable evidence is of major clinical importance. With thousands of endotracheal intubations performed every day in operating rooms around the world, every bit of performance improvement translates into increased patient safety and comfort and may eventually prevent significant burden of disease. Therefore, we feel confident that a large trial has the potential to considerably benefit patients and anaesthetists alike. Trial registration ClincalTrials.gov NCT05228288. Protocol version 1.1, November 15, 2021.},
  language  = {en}
}
@article{ZeinerSchroederMetzneretal.2023,
  author    = {Zeiner, Carsten and Schr{\"o}der, Malte and Metzner, Selina and Herrmann, Johannes and Notz, Quirin and Hottenrott, Sebastian and R{\"o}der, Daniel and Meybohm, Patrick and Lepper, Philipp M. and Lotz, Christopher},
  title     = {High-dose methylprednisolone pulse therapy during refractory COVID-19 acute respiratory distress syndrome: a retrospective observational study},
  series = {BMC Pulmonary Medicine},
  volume    = {23},
  journal   = {BMC Pulmonary Medicine},
  doi       = {10.1186/s12890-023-02664-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357231},
  year      = {2023},
  abstract  = {Background Current COVID-19 guidelines recommend the early use of systemic corticoids for COVID-19 acute respiratory distress syndrome (ARDS). It remains unknown if high-dose methylprednisolone pulse therapy (MPT) ameliorates refractory COVID-19 ARDS after many days of mechanical ventilation or rapid deterioration with or without extracorporeal membrane oxygenation (ECMO). Methods This is a retrospective observational study. Consecutive patients with COVID-19 ARDS treated with a parenteral high-dose methylprednisolone pulse therapy at the intensive care units (ICU) of two University Hospitals between January 1st 2021 and November 30st 2022 were included. Clinical data collection was at ICU admission, start of MPT, 3-, 10- and 14-days post MPT. Results Thirty-seven patients (mean age 55 ± 12 years) were included in the study. MPT started at a mean of 17 ± 12 days after mechanical ventilation. Nineteen patients (54\%) received ECMO support when commencing MPT. Mean paO2/FiO2 significantly improved 3- (p = 0.034) and 10 days (p = 0.0313) post MPT. The same applied to the necessary FiO2 10 days after MPT (p = 0.0240). There were no serious infectious complications. Twenty-four patients (65\%) survived to ICU discharge, including 13 out of 20 (65\%) needing ECMO support. Conclusions Late administration of high-dose MPT in a critical subset of refractory COVID-19 ARDS patients improved respiratory function and was associated with a higher-than-expected survival of 65\%. These data suggest that high-dose MPT may be a viable salvage therapy in refractory COVID-19 ARDS.},
  language  = {en}
}