@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{BianchiSivarajanWallesetal.2021, author = {Bianchi, Maria and Sivarajan, Rinu and Walles, Thorsten and Hackenberg, Stephan and Steinke, Maria}, title = {Susceptibility of primary human airway epithelial cells to Bordetella pertussis adenylate cyclase toxin in two- and three-dimensional culture conditions}, series = {Innate Immunity}, volume = {27}, journal = {Innate Immunity}, number = {1}, issn = {1753-4259}, doi = {10.1177/1753425920979354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219849}, pages = {89-98}, year = {2021}, abstract = {The human pathogen Bordetella pertussis targets the respiratory epithelium and causes whooping cough. Its virulence factor adenylate cyclase toxin (CyaA) plays an important role in the course of infection. Previous studies on the impact of CyaA on human epithelial cells have been carried out using cell lines derived from the airways or the intestinal tract. Here, we investigated the interaction of CyaA and its enzymatically inactive but fully pore-forming toxoid CyaA-AC- with primary human airway epithelial cells (hAEC) derived from different anatomical sites (nose and tracheo-bronchial region) in two-dimensional culture conditions. To assess possible differences between the response of primary hAEC and respiratory cell lines directly, we included HBEC3-KT in our studies. In comparative analyses, we studied the impact of both the toxin and the toxoid on cell viability, intracellular cAMP concentration and IL-6 secretion. We found that the selected hAEC, which lack CD11b, were differentially susceptible to both CyaA and CyaA-AC-. HBEC3-KT appeared not to be suitable for subsequent analyses. Since the nasal epithelium first gets in contact with airborne pathogens, we further studied the effect of CyaA and its toxoid on the innate immunity of three-dimensional tissue models of the human nasal mucosa. The present study reveals first insights in toxin-cell interaction using primary hAEC.}, language = {en} } @article{RotherKraftSmithetal.2021, author = {Rother, Lisa and Kraft, Nadine and Smith, Dylan B. and El Jundi, Basil and Gill, Richard J. and Pfeiffer, Keram}, title = {A micro-CT-based standard brain atlas of the bumblebee}, series = {Cell and Tissue Research}, volume = {386}, journal = {Cell and Tissue Research}, number = {1}, issn = {1432-0878}, doi = {10.1007/s00441-021-03482-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267783}, pages = {29-45}, year = {2021}, abstract = {In recent years, bumblebees have become a prominent insect model organism for a variety of biological disciplines, particularly to investigate learning behaviors as well as visual performance. Understanding these behaviors and their underlying neurobiological principles requires a clear understanding of brain anatomy. Furthermore, to be able to compare neuronal branching patterns across individuals, a common framework is required, which has led to the development of 3D standard brain atlases in most of the neurobiological insect model species. Yet, no bumblebee 3D standard brain atlas has been generated. Here we present a brain atlas for the buff-tailed bumblebee Bombus terrestris using micro-computed tomography (micro-CT) scans as a source for the raw data sets, rather than traditional confocal microscopy, to produce the first ever micro-CT-based insect brain atlas. We illustrate the advantages of the micro-CT technique, namely, identical native resolution in the three cardinal planes and 3D structure being better preserved. Our Bombus terrestris brain atlas consists of 30 neuropils reconstructed from ten individual worker bees, with micro-CT allowing us to segment neuropils completely intact, including the lamina, which is a tissue structure often damaged when dissecting for immunolabeling. Our brain atlas can serve as a platform to facilitate future neuroscience studies in bumblebees and illustrates the advantages of micro-CT for specific applications in insect neuroanatomy.}, language = {en} } @article{HoeslFroehlichPoschetal.2021, author = {Hoesl, Christine and Fr{\"o}hlich, Thomas and Posch, Christian and Kneitz, Hermann and Goebeler, Matthias and Schneider, Marlon R. and Dahlhoff, Maik}, title = {The transmembrane protein LRIG1 triggers melanocytic tumor development following chemically induced skin carcinogenesis}, series = {Molecular Oncology}, volume = {15}, journal = {Molecular Oncology}, number = {8}, doi = {10.1002/1878-0261.12945}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238925}, pages = {2140 -- 2155}, year = {2021}, abstract = {The incidence of melanoma and nonmelanoma skin cancer has increased tremendously in recent years. Although novel treatment options have significantly improved patient outcomes, the prognosis for most patients with an advanced disease remains dismal. It is, thus, imperative to understand the molecular mechanisms involved in skin carcinogenesis in order to develop new targeted treatment strategies. Receptor tyrosine kinases (RTK) like the ERBB receptor family, including EGFR/ERBB1, ERBB2/NEU, ERBB3, and ERBB4, are important regulators of skin homeostasis and their dysregulation often results in cancer, which makes them attractive therapeutic targets. Members of the leucine-rich repeats and immunoglobulin-like domains protein family (LRIG1-3) are ERBB regulators and thus potential therapeutic targets to manipulate ERBB receptors. Here, we analyzed the function of LRIG1 during chemically induced skin carcinogenesis in transgenic mice expressing LRIG1 in the skin under the control of the keratin 5 promoter (LRIG1-TG mice). We observed a significant induction of melanocytic tumor formation in LRIG1-TG mice and no difference in papilloma incidence between LRIG1-TG and control mice. Our findings also revealed that LRIG1 affects ERBB signaling via decreased phosphorylation of EGFR and increased activation of the oncoprotein ERBB2 during skin carcinogenesis. The epidermal proliferation rate was significantly decreased during epidermal tumorigenesis under LRIG1 overexpression, and the apoptosis marker cleaved caspase 3 was significantly activated in the epidermis of transgenic LRIG1 mice. Additionally, we detected LRIG1 expression in human cutaneous squamous cell carcinoma and melanoma samples. Therefore, we depleted LRIG1 in human melanoma cells (A375) by CRISPR/Cas9 technology and found that this caused EGFR and ERBB3 downregulation in A375 LRIG1 knockout cells 6 h following stimulation with EGF. In conclusion, our study demonstrated that LRIG1-TG mice develop melanocytic skin tumors during chemical skin carcinogenesis and a deletion of LRIG1 in human melanoma cells reduces EGFR and ERBB3 expression after EGF stimulation.}, language = {en} }