@article{LoebLinsmeierHerbertetal.2023, author = {L{\"o}b, Sanja and Linsmeier, Eva and Herbert, Saskia-Laureen and Schlaiß, Tanja and Kiesel, Matthias and Wischhusen, J{\"o}rg and Salmen, Jessica and Kranke, Peter and Quenzer, Anne and Kurz, Florian and Weiss, Claire and Gerhard-Hartmann, Elena and W{\"o}ckel, Achim and Diessner, Joachim}, title = {Prognostic effect of HER2 evolution from primary breast cancer to breast cancer metastases}, series = {Journal of Cancer Research and Clinical Oncology}, volume = {149}, journal = {Journal of Cancer Research and Clinical Oncology}, number = {8}, doi = {10.1007/s00432-022-04486-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324068}, pages = {5417-5428}, year = {2023}, abstract = {Purpose Therapeutic options for breast cancer (BC) treatment are constantly evolving. The Human Epidermal Growth Factor 2 (HER2)-low BC entity is a new subgroup, representing about 55\% of all BC patients. New antibody-drug conjugates demonstrated promising results for this BC subgroup. Currently, there is limited information about the conversion of HER2 subtypes between primary tumor and recurrent disease. Methods This retrospective study included women with BC at the University Medical Centre Wuerzburg from 1998 to 2021. Data were retrieved from patients' records. HER2 evolution from primary diagnosis to the first relapse and the development of secondary metastases was investigated. Results In the HR-positive subgroup without HER2 overexpression, HER2-low expression in primary BC was 56.7 vs. 14.6\% in the triple-negative subgroup (p < 0.000). In the cohort of the first relapse, HER2-low represented 64.1\% of HR-positive vs. 48.2\% of the triple-negative cohort (p = 0.03). In patients with secondary metastases, HER2-low was 75.6\% vs. 50\% in the triple negative subgroup (p = 0.10). The subgroup of HER2-positive breast cancer patients numerically increased in the course of disease; the HER2-negative overall cohort decreased. A loss of HER2 expression from primary BC to the first relapse correlated with a better OS (p = 0.018). No clinicopathological or therapeutic features could be identified as potential risk factors for HER2 conversion. Conclusion HER2 expression is rising during the progression of BC disease. In view of upcoming therapeutical options, the re-analysis of newly developed metastasis will become increasingly important.}, language = {en} } @article{HolzmannLittigStadlerPoppetal.2023, author = {Holzmann-Littig, Christopher and Stadler, David and Popp, Maria and Kranke, Peter and Fichtner, Falk and Schmaderer, Christoph and Renders, Lutz and Braunisch, Matthias Christoph and Assali, Tarek and Platen, Louise and Wijnen-Meijer, Marjo and L{\"u}hnen, Julia and Steckelberg, Anke and Pfadenhauer, Lisa and Haller, Bernhard and Fuetterer, Cornelia and Seeber, Christian and Schaaf, Christian}, title = {Locating medical information during an infodemic: information seeking behavior and strategies of health-care workers in Germany}, series = {Healthcare}, volume = {11}, journal = {Healthcare}, number = {11}, issn = {2227-9032}, doi = {10.3390/healthcare11111602}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319306}, year = {2023}, abstract = {Background: The COVID-19 pandemic has led to a flood of — often contradictory — evidence. HCWs had to develop strategies to locate information that supported their work. We investigated the information-seeking of different HCW groups in Germany. Methods: In December 2020, we conducted online surveys on COVID-19 information sources, strategies, assigned trustworthiness, and barriers — and in February 2021, on COVID-19 vaccination information sources. Results were analyzed descriptively; group comparisons were performed using χ\(^2\)-tests. Results: For general COVID-19-related medical information (413 participants), non-physicians most often selected official websites (57\%), TV (57\%), and e-mail/newsletters (46\%) as preferred information sources — physicians chose official websites (63\%), e-mail/newsletters (56\%), and professional journals (55\%). Non-physician HCWs used Facebook/YouTube more frequently. The main barriers were insufficient time and access issues. Non-physicians chose abstracts (66\%), videos (45\%), and webinars (40\%) as preferred information strategy; physicians: overviews with algorithms (66\%), abstracts (62\%), webinars (48\%). Information seeking on COVID-19 vaccination (2700 participants) was quite similar, however, with newspapers being more often used by non-physicians (63\%) vs. physician HCWs (70\%). Conclusion: Non-physician HCWs more often consulted public information sources. Employers/institutions should ensure the supply of professional, targeted COVID-19 information for different HCW groups.}, 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{WernerPoppFichtneretal.2022, author = {Werner, Anne and Popp, Maria and Fichtner, Falk and Holzmann-Littig, Christopher and Kranke, Peter and Steckelberg, Anke and L{\"u}hnen, Julia and Redlich, Lisa Marie and Dickel, Steffen and Grimm, Clemens and Moerer, Onnen and Nothacker, Monika and Seeber, Christian}, title = {COVID-19 intensive care — Evaluation of public information sources and current standards of care in German intensive care units: a cross sectional online survey on intensive care staff in Germany}, series = {Healthcare}, volume = {10}, journal = {Healthcare}, number = {7}, issn = {2227-9032}, doi = {10.3390/healthcare10071315}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281865}, year = {2022}, abstract = {Backround: In February 2021, the first formal evidence and consensus-based (S3) guidelines for the inpatient treatment of patients with COVID-19 were published in Germany and have been updated twice during 2021. The aim of the present study is to re-evaluate the dissemination pathways and strategies for ICU staff (first evaluation in December 2020 when previous versions of consensus-based guidelines (S2k) were published) and question selected aspects of guideline adherence of standard care for patients with COVID-19 in the ICU. Methods: We conducted an anonymous online survey among German intensive care staff from 11 October 2021 to 11 November 2021. We distributed the survey via e-mail in intensive care facilities and requested redirection to additional intensive care staff (snowball sampling). Results: There was a difference between the professional groups in the number, selection and qualitative assessment of information sources about COVID-19. Standard operating procedures were most frequently used by all occupational groups and received a high quality rating. Physicians preferred sources for active information search (e.g., medical journals), while nurses predominantly used passive consumable sources (e.g., every-day media). Despite differences in usage behaviour, the sources were rated similarly in terms of the quality of the information on COVID-19. The trusted organizations have not changed over time. The use of guidelines was frequently stated and highly recommended. The majority of the participants reported guideline-compliant treatment. Nevertheless, there were certain variations in the use of medication as well as the criteria chosen for discontinuing non-invasive ventilation (NIV) compared to guideline recommendations. Conclusions: An adequate external source of information for nursing staff is lacking, the usual sources of physicians are only appropriate for the minority of nursing staff. The self-reported use of guidelines is high.}, language = {en} } @article{HolzmannLittigFrankSchmadereretal.2022, author = {Holzmann-Littig, Christopher and Frank, Tamara and Schmaderer, Christoph and Braunisch, Matthias C. and Renders, Lutz and Kranke, Peter and Popp, Maria and Seeber, Christian and Fichtner, Falk and Littig, Bianca and Carbajo-Lozoya, Javier and Meerpohl, Joerg J. and Haller, Bernhard and Allwang, Christine}, title = {COVID-19 Vaccines: Fear of side effects among German health care workers}, series = {Vaccines}, volume = {10}, journal = {Vaccines}, number = {5}, issn = {2076-393X}, doi = {10.3390/vaccines10050689}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270561}, year = {2022}, abstract = {(1) Background: Health care workers (HCWs) play a key role in increasing anti-COVID vaccination rates. Fear of potential side effects is one of the main reasons for vaccine hesitancy. We investigated which side effects are of concern to HCWs and how these are associated with vaccine hesitancy. (2) Methods: Data were collected in an online survey in February 2021 among HCWs from across Germany with 4500 included participants. Free-text comments on previously experienced vaccination side effects, and fear of short- and long-term side effects of the COVID-19 vaccination were categorized and analyzed. (3) Results: Most feared short-term side effects were vaccination reactions, allergic reactions, and limitations in daily life. Most feared long-term side effects were (auto-) immune reactions, neurological side effects, and currently unknown long-term consequences. Concerns about serious vaccination side effects were associated with vaccination refusal. There was a clear association between refusal of COVID-19 vaccination in one's personal environment and fear of side effects. (4) Conclusions: Transparent information about vaccine side effects is needed, especially for HCW. Especially when the participants' acquaintances advised against vaccination, they were significantly more likely to fear side effects. Thus, further education of HCW is necessary to achieve good information transfer in clusters as well.}, 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{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{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{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{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{HolzmannLittigBraunischKrankeetal.2021, author = {Holzmann-Littig, Christopher and Braunisch, Matthias Christoph and Kranke, Peter and Popp, Maria and Seeber, Christian and Fichtner, Falk and Littig, Bianca and Carbajo-Lozoya, Javier and Allwang, Christine and Frank, Tamara and Meerpohl, Joerg Johannes and Haller, Bernhard and Schmaderer, Christoph}, title = {COVID-19 vaccination acceptance and hesitancy among healthcare workers in germany}, series = {Vaccines}, volume = {9}, journal = {Vaccines}, number = {7}, issn = {2076-393X}, doi = {10.3390/vaccines9070777}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242627}, year = {2021}, abstract = {Vaccination hesitancy is a threat to herd immunity. Healthcare workers (HCWs) play a key role in promoting Coronavirus disease 2019 (COVID-19) vaccination in the general population. We therefore aimed to provide data on COVID-19 vaccination acceptance/hesitancy among German HCWs. For this exploratory, cross-sectional study, an online survey was conducted in February 2021. The survey included 54 items on demographics; previous vaccination behavior; trust in vaccines, physicians, the pharmaceutical industry and health politics; fear of adverse effects; assumptions regarding the consequences of COVID-19; knowledge about vaccines; and information seeking behavior. Odds ratios with 95\% confidence intervals were calculated and chi-square tests were performed. Four thousand five hundred surveys were analyzed. The overall vaccination acceptance was 91.7\%. The age group ≤20 years showed the lowest vaccination acceptance. Factors associated with vaccination hesitancy were lack of trust in authorities and pharmaceutical companies. Attitudes among acquaintances were associated with vaccination hesitancy too. Participants with vaccination hesitancy more often obtained information about COVID-19 vaccines via messenger services or online video platforms and underperformed in the knowledge test. We found high acceptance amongst German HCWs. Several factors associated with vaccination hesitancy were identified which could be targeted in HCW vaccination campaigns.}, 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{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{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{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{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{HinkelbeinIovinoDeRobertisetal.2019, author = {Hinkelbein, Jochen and Iovino, Ivan and De Robertis, Edoardo and Kranke, Peter}, title = {Outcomes in video laryngoscopy studies from 2007 to 2017: systematic review and analysis of primary and secondary endpoints for a core set of outcomes in video laryngoscopy research}, series = {BMC Anesthesiology}, volume = {19}, journal = {BMC Anesthesiology}, doi = {10.1186/s12871-019-0716-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320747}, year = {2019}, abstract = {Background Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However, high-quality research is rarely published and studies usually have different primary or secondary endpoints which impedes clear unbiased comparisons between studies. The aim of the present study was to gather and analyse primary and secondary endpoints in video laryngoscopy studies being published over the last ten years and to create a core set of uniform or homogeneous outcomes (COS). Methods Retrospective analysis. Data were identified by using MEDLINE® database and the terms "video laryngoscopy" and "video laryngoscope" limited to the years 2007 to 2017. A total of 3351 studies were identified by the applied search strategy in PubMed. Papers were screened by two anaesthesiologists independently to identify study endpoints. The DELPHI method was used for consensus finding. Results In the 372 studies analysed and included, 49 different outcome categories/columns were reported. The items "time to intubation" (65.86\%), "laryngeal view grade" (44.89\%), "successful intubation rate" (36.56\%), "number of intubation attempts" (23.39\%), "complications" (21.24\%), and "successful first-pass intubation rate" (19.09\%) were reported most frequently. A total of 19 specific parameters is recommended. Conclusions In recent video laryngoscopy studies, many different and inhomogeneous parameters were used as outcome descriptors/endpoints. Based on these findings, we recommend that 19 specific parameters (e.g., "time to intubation" (inserting the laryngoscope to first ventilation), "laryngeal view grade" (C\&L and POGO), "successful intubation rate", etc.) should be used in coming research to facilitate future comparisons of video laryngoscopy studies.}, language = {en} } @article{SaundersDavisKrankeetal.2018, author = {Saunders, Rhodri and Davis, Jason A. and Kranke, Peter and Weissbrod, Rachel and Whitaker, David K and Lightdale, Jenifer R}, title = {Clinical and economic burden of procedural sedation-related adverse events and their outcomes: analysis from five countries}, series = {Therapeutics and Clinical Risk Management}, volume = {14}, journal = {Therapeutics and Clinical Risk Management}, doi = {10.2147/TCRM.S154720}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227508}, pages = {393-401}, year = {2018}, abstract = {Background: Studies have reported on the incidence of sedation-related adverse events (AEs), but little is known about their impact on health care costs and resource use. Methods: Health care providers and payers in five countries were recruited for an online survey by independent administrators to ensure that investigators and respondents were blinded to each other. Surveys were conducted in the local language and began with a "screener" to ensure that respondents had relevant expertise and experience. Responses were analyzed using Excel and R, with the Dixon's Q statistic used to identify and remove outliers. Global and country-specific average treatment patterns were calculated via bootstrapping; costs were mean values. The sum product of costs and intervention probability gave a cost per AE. Results: Responses were received from 101 providers and 26 payers, the majority having. 5 years of experience. At a minimum, the respondents performed a total of 3,430 procedural sedations per month. All AEs detailed occurred in clinical practice in the last year and were reported to cause procedural delays and cancellations in some patients. Standard procedural sedation costs ranged from (sic)74 (Germany) to \$2,300 (US). Respondents estimated that AEs would increase costs by between 16\% (Italy) and 179\% (US). Hypotension was reported as the most commonly observed AE with an associated global mean cost (interquartile range) of \$43 (\$27-\$68). Other frequent AEs, including mild hypotension, bradycardia, tachycardia, mild oxygen desaturation, hypertension, and brief apnea, were estimated to increase health care spending on procedural sedation by \$2.2 billion annually in the US. Conclusion: All sedation-related AEs can increase health care costs and result in substantial delays or cancellations of subsequent procedures. The prevention of even minor AEs during procedural sedation may be crucial to ensuring its value as a health care service.}, language = {en} } @article{MarxSchindlerMoschetal.2016, author = {Marx, Gernot and Schindler, Achim W. and Mosch, Christoph and Albers, Joerg and Bauer, Michael and Gnass, Irmela and Hobohm, Carsten and Janssens, Uwe and Kluge, Stefan and Kranke, Peter and Maurer, Tobias and Merz, Waltraut and Neugebauer, Edmund and Quintel, Michael and Senninger, Norbert and Trampisch, Hans-Joachim and Waydhas, Christian and Wildenauer, Rene and Zacharowski, Kai and Eikermann, Michaela}, title = {Intravascular volume therapy in adults guidelines from the association of the scientific medical societies in Germany}, series = {European Journal of Anaesthesiology}, volume = {33}, journal = {European Journal of Anaesthesiology}, number = {7}, doi = {10.1097/EJA.0000000000000447}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188223}, pages = {488-521}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{KurrekMorganHowardetal.2015, author = {Kurrek, Matt M. and Morgan, Pamela and Howard, Steven and Kranke, Peter and Calhoun, Aaron and Hui, Joshua and Kiss, Alex}, title = {Simulation as a New Tool to Establish Benchmark Outcome Measures in Obstetrics}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0131064}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151646}, pages = {e0131064}, year = {2015}, abstract = {Background There are not enough clinical data from rare critical events to calculate statistics to decide if the management of actual events might be below what could reasonably be expected (i.e. was an outlier). Objectives In this project we used simulation to describe the distribution of management times as an approach to decide if the management of a simulated obstetrical crisis scenario could be considered an outlier. Design Twelve obstetrical teams managed 4 scenarios that were previously developed. Relevant outcome variables were defined by expert consensus. The distribution of the response times from the teams who performed the respective intervention was graphically displayed and median and quartiles calculated using rank order statistics. Results Only 7 of the 12 teams performed chest compressions during the arrest following the 'cannot intubate/cannot ventilate' scenario. All other outcome measures were performed by at least 11 of the 12 teams. Calculation of medians and quartiles with 95\% CI was possible for all outcomes. Confidence intervals, given the small sample size, were large. Conclusion We demonstrated the use of simulation to calculate quantiles for management times of critical event. This approach could assist in deciding if a given performance could be considered normal and also point to aspects of care that seem to pose particular challenges as evidenced by a large number of teams not performing the expected maneuver. However sufficiently large sample sizes (i.e. from a national data base) will be required to calculate acceptable confidence intervals and to establish actual tolerance limits.}, language = {en} } @article{MuellenbachRoewerKranke2013, author = {M{\"u}llenbach, Ralf Michael and Roewer, Norbert and Kranke, Peter}, title = {Quality Assurance Would Be Welcome}, series = {Deutsches {\"A}rzteblatt international}, volume = {110}, journal = {Deutsches {\"A}rzteblatt international}, number = {27-28}, doi = {10.3238/arztebl.2013.0485a}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128844}, pages = {485}, year = {2013}, abstract = {No abstract available.}, language = {en} } @article{KrankeGirardLavand’hommeetal.2013, author = {Kranke, Peter and Girard, Thierry and Lavand'homme, Patricia and Melber, Andrea and Jokinen, Johanna and Muellenbach, Ralf M. and Wirbelauer, Johannes and H{\"o}nig, Arnd}, title = {Must we press on until a young mother dies? Remifentanil patient controlled analgesia in labour may not be suited as a "poor man's epidural"}, series = {BMC Pregnancy and Childbirth}, journal = {BMC Pregnancy and Childbirth}, doi = {10.1186/1471-2393-13-139}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96262}, year = {2013}, abstract = {Background The epidural route is still considered the gold standard for labour analgesia, although it is not without serious consequences when incorrect placement goes unrecognized, e.g. in case of intravascular, intrathecal and subdural placements. Until now there has not been a viable alternative to epidural analgesia especially in view of the neonatal outcome and the need for respiratory support when long-acting opioids are used via the parenteral route. Pethidine and meptazinol are far from ideal having been described as providing rather sedation than analgesia, affecting the cardiotocograph (CTG), causing fetal acidosis and having active metabolites with prolonged half-lives especially in the neonate. Despite these obvious shortcomings, intramuscular and intravenously administered pethidine and comparable substances are still frequently used in delivery units. Since the end of the 90ths remifentanil administered in a patient-controlled mode (PCA) had been reported as a useful alternative for labour analgesia in those women who either don't want, can't have or don't need epidural analgesia. Discussion In view of the need for conversion to central neuraxial blocks and the analgesic effect remifentanil has been demonstrated to be superior to pethidine. Despite being less effective in terms of the resulting pain scores, clinical studies suggest that the satisfaction with analgesia may be comparable to that obtained with epidural analgesia. Owing to this fact, remifentanil has gained a place in modern labour analgesia in many institutions. However, the fact that remifentanil may cause harm should not be forgotten when the use of this potent mu-agonist is considered for the use in labouring women. In the setting of one-to-one midwifery care, appropriate monitoring and providing that enough experience exists with this potent opioid and the treatment of potential complications, remifentanil PCA is a useful option in addition to epidural analgesia and other central neuraxial blocks. Already described serious consequences should remind us not refer to remifentanil PCA as a "poor man's epidural" and to safely administer remifentanil with an appropriate indication. Summary Therefore, the authors conclude that economic considerations and potential cost-savings in conjunction with remifentanil PCA may not be appropriate main endpoints when studying this valuable method for labour analgesia.}, language = {en} } @article{BrevoordKrankeKuijpersetal.2012, author = {Brevoord, Daniel and Kranke, Peter and Kuijpers, Marijn and Weber, Nina and Hollmann, Markus and Preckel, Benedikt}, title = {Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {7}, doi = {10.1371/journal.pone.0042179}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134471}, pages = {e42179}, year = {2012}, abstract = {Background: Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury. Methods and Results: Medline, EMBASE and Cochrane databases were searched for randomized clinical trials comparing remote ischemic conditioning, regardless of timing, with no conditioning. Two investigators independently selected suitable trials, assessed trial quality and extracted data. 23 studies in patients undergoing cardiac surgery (15 studies), percutaneous coronary intervention (four studies) and vascular surgery (four studies), comprising in total 1878 patients, were included in this review. Compared to no conditioning, remote ischemic conditioning did not reduce mortality (odds ratio 1.22 [95\% confidence interval 0.48, 3.07]) or major adverse cardiovascular events (0.65 [0.38, 1.14]). However, the incidence of myocardial infarction was reduced with remote ischemic conditioning (0.50 [0.31, 0.82]), as was peak troponin release (standardized mean difference -0.28 [-0.47, -0.09]). Conclusion: There is no evidence that remote ischemic conditioning reduces mortality associated with ischemic events; nor does it reduce major adverse cardiovascular events. However, remote ischemic conditioning did reduce the incidence of peri-procedural myocardial infarctions, as well as the release of troponin.}, language = {en} } @article{WahlenRoewerKranke2010, author = {Wahlen, Bianca M. and Roewer, Norbert and Kranke, Peter}, title = {Use of local anaesthetics and adjuncts for spinal and epidural anaesthesia and analgesia at German and Austrian University Hospitals: an online survey to access current standard practice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67847}, year = {2010}, abstract = {Background: The present anonymous multicenter online survey was conducted to evaluate the application of regional anaesthesia techniques as well as the used local anaesthetics and adjuncts at German and Austrian university hospitals. Methods: 39 university hospitals were requested to fill in an online questionnaire, to determine the kind of regional anaesthesia and preferred drugs in urology, obstetrics and gynaecology. Results: 33 hospitals responded. No regional anaesthesia is conducted in 47\% of the minor gynaecological and 44\% of the urological operations; plain bupivacaine 0.5\% is used in 38\% and 47\% respectively. In transurethral resections of the prostate and bladder no regional anaesthesia is used in 3\% of the responding hospitals, whereas plain bupivacaine 0.5\% is used in more than 90\%. Regional anaesthesia is only used in selected major gynaecological and urological operations. On the contrary to the smaller operations, the survey revealed a large variety of used drugs and mixtures. Almost 80\% prefer plain bupivacaine or ropivacaine 0.5\% in spinal anaesthesia in caesarean section. Similarly to the use of drugs in major urological and gynaecological operations a wide range of drugs and adjuncts is used in epidural anaesthesia in caesarean section and spontaneous delivery. Conclusions: Our results indicate a certain agreement in short operations in spinal anaesthesia. By contrast, a large variety concerning the anaesthesiological approach in larger operations as well as in epidural analgesia in obstetrics could be revealed, the causes of which are assumed to be primarily rooted in particular departmental structures.}, subject = {An{\"a}sthesiologie}, language = {en} } @article{RueschEberhartWallenbornetal.2010, author = {Ruesch, Dirk and Eberhart, Leopold H. J. and Wallenborn, Jan and Kranke, Peter}, title = {Nausea and Vomiting After Surgery Under General Anesthesia An Evidence-Based Review Concerning Risk Assessment, Prevention, and Treatment}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85847}, year = {2010}, abstract = {Background: The German-language recommendations for the management of postoperative nausea and vomiting(PONV) have been revised by an expert committee. Major aspects of this revision are presented here in the form of an evidence-based review article. Methods: The literature was systematically reviewed with the goal of revising the existing recommendations. New evidence-based recommendations for the management of PONV were developed, approved by consensus, and graded according to the scheme of the Scottish Intercollegiate Guidelines Network (SIGN). Results: The relevant risk factors for PONV include female sex, nonsmoker status, prior history of PONV, motion sickness, use of opioids during and after surgery, use of inhalational anesthetics and nitrous oxide, and the duration of anesthesia. PONV scoring systems provide a rough assessment of risk that can serve as the basis for a riskadapted approach. Risk-adapted prophylaxis, however, has not been shown to provide any greater benefit than fixed (combination) prophylaxis, and PONV risk scores have inherent limitations; thus, fixed prophylaxis may be advantageous. Whichever of these two approaches to manage PONV is chosen, high-risk patients must be given multimodal prophylaxis, involving both the avoidance of known risk factors and the application of multiple validated and effective antiemetic interventions. PONV should be treated as soon as it arises, to minimize patient discomfort, the risk of medical complications, and the costs involved. Conclusion: PONV lowers patient satisfaction but is treatable. The effective, evidence-based measures of preventing and treating it should be implemented in routine practice.}, language = {en} }