@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{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{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{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{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{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{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{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{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} }