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Nitro-fatty acids (NFAs) are endogenous lipid mediators causing a spectrum of anti-inflammatory effects by covalent modification of key proteins within inflammatory signaling pathways. Recent animal models of solid tumors have helped demonstrate their potential as anti-tumorigenic therapeutics. This study evaluated the anti-tumorigenic effects of NFAs in colon carcinoma cells and other solid and leukemic tumor cell lines. NFAs inhibited the ubiquitin-proteasome system (UPS) by directly targeting the 26S proteasome, leading to polyubiquitination and inhibition of the proteasome activities. UPS suppression induced the unfolded protein response, resulting in tumor cell death. The NFA-mediated effects were substantial, specific, and enduring, representing a unique mode of action for UPS suppression. This study provides mechanistic insights into the biological actions of NFAs as possible endogenous tumor-suppressive factors, indicating that NFAs might be key structures for designing a novel class of direct proteasome inhibitors., Competing Interests: Declaration of interests The authors declare no potential conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) therapy is rapidly expanding worldwide, yet this therapy has a serious risk of bleeding. Whether coagulation-activating viral infections such as COVID-19 may have an impact on the risk of bleeding is largely unknown. This study conducted a monocentric investigation of severely affected COVID-19 patients receiving VV-ECMO therapy with regard to the occurrence and possible influences of minor and major bleeding and transfusion requirements. Among the 114 included study patients, we were able to assess more than 74,000 h of VV-ECMO therapy. In these, 103 major bleeding events and 2283 minor bleeding events were detected. In total, 1396 red blood concentrates (RBCs) were administered. A statistically significant correlation with the applied anticoagulation or demographic data of the patients was not observed. Contrary to the frequently observed thromboembolic complications among COVID-19 patients, patients with VV-ECMO therapy, even under low-dose anticoagulation, show a distinct bleeding profile, especially of minor bleeding, with a substantial need for blood transfusions. COVID-19 patients show a tendency to have frequent bleeding and require repeated RBC transfusions during VV-ECMO. This fact might not be solely explained by the mechanical alteration of ECMO or anticoagulation.

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Blood gas analysis plays a central role in modern medicine. Advances in technology have expanded the range of available parameters and increased the complexity of their interpretation. By applying user-centered design principles, it is possible to reduce the cognitive load associated with interpreting blood gas analysis. In this international, multicenter study, we explored anesthesiologists' perspectives on Visual Blood, a novel visualization technique for presenting blood gas analysis results. We conducted interviews with participants following two computer-based simulation studies, the first utilizing virtual reality (VR) (50 participants) and the second without VR (70 participants). Employing the template approach, we identified key themes in the interview responses and formulated six statements, which were rated using Likert scales from 1 (strongly disagree) to 5 (strongly agree) in an online questionnaire. The most frequently mentioned theme was the positive usability features of Visual Blood. The online survey revealed that participants found Visual Blood to be an intuitive method for interpreting blood gas analysis (median 4, interquartile range (IQR) 4-4, p < 0.001). Participants noted that minimal training was required to effectively learn how to interpret Visual Blood (median 4, IQR 4-4, p < 0.001). However, adjustments are necessary to reduce visual overload (median 4, IQR 2-4, p < 0.001). Overall, Visual Blood received a favorable response. The strengths and weaknesses derived from these data will help optimize future versions of Visual Blood to improve the presentation of blood gas analysis results.

Background: The epidural catheter for analgesia has been used for decades and has become the gold standard in pain therapy for pregnant women in labour. However, procedural parameters such as time to pain relief and duration to implementation pose hurdles for patients shortly before delivery. Low-dose spinal analgesia (LDSA) is an alternative procedure that was investigated in the study with regard to patient satisfaction and complication rates compared to epidural catheter., Methods: In a retrospective monocentric study, a total of 242 patients receiving low-dose spinal analgesia or epidural catheters were evaluated using propensity score matching. Subjective patient satisfaction as well as complication rates were primarily analysed. We hypothesise that LDSA is a safe procedure and provides a similar level of satisfaction compared with the epidural catheter. For this purpose, both procedures were performed according to in-house standards and the patients were interviewed afterwards. Patients who required surgical delivery were excluded to prevent bias., Results: The LDSA was rated on average as very good [1.09 ± 0.311 vs. 1.07 ± 0.431] in terms of satisfaction by the patients compared to the epidural catheter without showing a significant difference ( p = 0.653). Complications were in the low single-digit non-significant range for both procedures [6 (5%) vs. 7 (6%); p = 0.776]. The evaluation showed more perineal tears I° and II° in the low-dose spinal analgesia group [I°: 28 (23%) vs. 3 (2%); p < 0.001-II°: 30 (25%) vs. 2 (2%); p < 0.001]. Neonatal parameters differed significantly only in umbilical cord base excess and umbilical cord venous pH [-5.40 vs. -6.40; p = 0.005]., Conclusions: LDSA represents a low complication procedure for patients at the end of labour with a high satisfaction level. With the LDSA in the repertoire of pain relief during childbirth, it is possible to also achieve pain reduction for women with deliveries of high velocity without compromising patient satisfaction or perinatal morbidity.

Advanced chronic liver disease is accompanied with relevant changes in the corpuscular and plasmatic coagulation system. Due to thrombocytopenia that is regularly observed in these patients, platelet transfusions are often performed prior invasive procedures to prevent possible bleeding complications. However, platelet transfusions are associated with clinically significant adverse events and economically relevant health care costs. Thus, avoiding unnecessary platelet transfusions remains pivotal in daily clinical practice. The first step is to carefully check if increasing platelet counts prior to a planned invasive procedure is really necessary. Nowadays, two well-tolerated thrombopoetin-receptor agonists (TPO-RAs), Avatrombopaq and Lusutrombopaq, to treat thrombocytopenia preemptively before an invasive procedure in patients with liver cirrhosis are available. This review provides a guide for clinician when to increase platelet counts prior an invasive procedure in patients with liver cirrhosis and helps to identify situations in which the use of TPO-RA may be reasonable., Competing Interests: Die Grundlagen des Expertenkonsens wurden im Rahmen eines Advisory Boards diskutiert, welches von Sobi gesponsert wurde., (Thieme. All rights reserved.)

Background: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated., Methods: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay., Results: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001)., Conclusions: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion., Clinical Trial Registration: NCT02147795., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Cardiac arrest in a modern intensive care unit (ICU) is associated with poor outcome although optimal resources are present at all times. Data on cardiac arrest (CA) of the increasing cohort of patients with veno-venous-extracorporeal membrane oxygenation (VV-ECMO) are not available. Due to the highly invasive nature of this procedure, other incidences and causes of cardiac arrest are expected when compared to the ICU population without ECMO. This study focuses on cardiac arrest under VV-ECMO treatment., Methods: Retrospective single-center observational study including all VV-ECMO patients from 1st January 2019 until 31st March 2022. Primary focus of this study was number and causes for CA during VV-ECMO treatment. Secondary endpoints were treatment procedure, complications and outcome., Results: 140 patients were treated with VV-ECMO in the study period. Of those, 23 patients had 29 CA with need for cardiopulmonary resuscitation (CPR) during VV-ECMO treatment. Nearly half of all CA (48%; n = 14) occurred during medical procedures and 21% (n = 6) were device related. Pulseless electric activity (PEA) was the most common rhythm upon CPR initiation (72%). ROSC was achieved in 86%, two CA (6.9%) resulted in extracorporeal CPR. Survival to hospital discharge was 13% following CPR., Conclusion: CA occurs in over 15% of all patients treated with a VV-ECMO. Medical procedures during VV-ECMO are associated with a high risk of CA and should be planned with care. Also, the rate of ROSC was very high, only a small number of patients survived the overall VV-ECMO treatment course., Competing Interests: A.N.F. received speaker fees from P.J. Dahlhausen & Co. GmbH, Cologne, Germany, received the Sedana Medical Research Grant 2020 and Thieme Teaching Award 2022. E.H.A. received a research grant of the German Research Foundation (AD 592/1-1) F.J.R received speaker fees from Helios Germany, university hospital Würzburg and Keller Medical GmbH. FJR received financial support by HemoSonics LLC, pharma-consult Petersohn and Boehringer Ingelheim. K.Z. has received honoraria for participation in advisory board meetings for Haemonetics and Vifor and received speaker fees from CSL Behring and GE Healthcare. He is the Principal Investigator of the EU-Horizon 2020 project ENVISION (Intelligent plug-and-play digital tool for real-time surveillance of COVID-19 patients and smart decision-making in Intensive Care Units). F.B. & H.B. declare that there are no conflicts of interest. The other authors declare that there are no conflicts of interest.This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Booke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Drowning is one of the leading causes of death worldwide and presents with a wide range of symptoms, from simple coughing to cardiac or pulmonary failure. In severe cases, extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy. Therefore, we sought to analyse ECMO usage, outcomes and predictive factors in drowned patients., Methods: The Federal Statistical Office of Germany provided the study data. The patients included experienced drowning (ICD T75.1) and ECMO (OPS 8-852.0, 8-852.3) between 2007 and 2020. All age groups were included. Mortality was calculated for the total population and for ECMO patients. A multiple logistic regression model for ECMO patients was applied to account for predefined patient characteristics and complications., Results: Of 12,354 patients who were hospitalised due to drowning, 237 patients (1.9%) received ECMO. Hospital mortality was 14.1% (n = 1741) overall and 74.7% (n = 177) for ECMO patients. In-hospital mortality was positively associated with cardiopulmonary resuscitation (CPR) before admission (odds ratio [OR] 4.49, 1.31-15.39) and in-hospital CPR (OR 6.28, 2.76-14.31). Stroke (OR 0.14, 0.02-0.96) and drug abuse (OR 0.05, 0.01-0.45) were negatively associated with in-hospital mortality. Neither the ECMO mode nor the patient's age and sex had statistically significant effects on survival., Conclusion: This study indicates that survival in drowned patients who receive ECMO is lower than previously reported. The proportion of paediatric patients was also smaller than expected. As the effects of different ECMO modes on mortality remain unclear, the need for further study remains great., (© 2023. The Author(s).)

Aims: To establish a set of quality indicators (QIs) for the cardiovascular (CV) assessment and management of patients undergoing non-cardiac surgery (NCS)., Methods and Results: The Quality Indicator Committee of the European Society of Cardiology (ESC) and European Society of Anaesthesiology and Intensive Care (ESAIC) in collaboration with Task Force members of the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS followed the ESC methodology for QI development. This included (1) identification, by constructing a conceptual framework of care, of domains of the CV assessment, and management of patients with risk factors or established cardiovascular disease (CVD) who are considered for or undergoing NCS, (2) development of candidate QIs following a systematic literature review, (3) selection of the final set of QIs using a modified Delphi method, and (4) evaluation of the feasibility of the developed QIs. In total, eight main and nine secondary QIs were selected across six domains: (1) structural framework (written policy), (2) patient education and quality of life (CV risk discussion), (3) peri-operative risk assessment (indication for diagnostic tests), (4) peri-operative risk mitigation (use of hospital therapies), (5) follow-up (post-discharge assessment), and (6) outcomes (major CV events)., Conclusion: We present the 2022 ESC/ESAIC QIs for the CV assessment and management of patients with risk factors or established CVD who are considered for or are undergoing NCS y. These indicators are supported by evidence from the literature, underpinned by expert consensus, and align with the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Artificial intelligence (AI) applications offer numerous opportunities to improve health care. To be used in the intensive care unit, AI must meet the needs of staff, and potential barriers must be addressed through joint action by all stakeholders. It is thus critical to assess the needs and concerns of anesthesiologists and intensive care physicians related to AI in health care throughout Europe., Objective: This Europe-wide, cross-sectional observational study investigates how potential users of AI systems in anesthesiology and intensive care assess the opportunities and risks of the new technology. The web-based questionnaire was based on the established analytic model of acceptance of innovations by Rogers to record 5 stages of innovation acceptance., Methods: The questionnaire was sent twice in 2 months (March 11, 2021, and November 5, 2021) through the European Society of Anaesthesiology and Intensive Care (ESAIC) member email distribution list. A total of 9294 ESAIC members were reached, of whom 728 filled out the questionnaire (response rate 728/9294, 8%). Due to missing data, 27 questionnaires were excluded. The analyses were conducted with 701 participants., Results: A total of 701 questionnaires (female: n=299, 42%) were analyzed. Overall, 265 (37.8%) of the participants have been in contact with AI and evaluated the benefits of this technology higher (mean 3.22, SD 0.39) than participants who stated no previous contact (mean 3.01, SD 0.48). Physicians see the most benefits of AI application in early warning systems (335/701, 48% strongly agreed, and 358/701, 51% agreed). Major potential disadvantages were technical problems (236/701, 34% strongly agreed, and 410/701, 58% agreed) and handling difficulties (126/701, 18% strongly agreed, and 462/701, 66% agreed), both of which could be addressed by Europe-wide digitalization and education. In addition, the lack of a secure legal basis for the research and use of medical AI in the European Union leads doctors to expect problems with legal liability (186/701, 27% strongly agreed, and 374/701, 53% agreed) and data protection (148/701, 21% strongly agreed, and 343/701, 49% agreed)., Conclusions: Anesthesiologists and intensive care personnel are open to AI applications in their professional field and expect numerous benefits for staff and patients. Regional differences in the digitalization of the private sector are not reflected in the acceptance of AI among health care professionals. Physicians anticipate technical difficulties and lack a stable legal basis for the use of AI. Training for medical staff could increase the benefits of AI in professional medicine. Therefore, we suggest that the development and implementation of AI in health care require a solid technical, legal, and ethical basis, as well as adequate education and training of users., (©Jan Andreas Kloka, Sophie C Holtmann, Elina Nürenberg-Goloub, Florian Piekarski, Kai Zacharowski, Benjamin Friedrichson. Originally published in JMIR Formative Research (https://formative.jmir.org), 12.06.2023.)

Background: In the context of the coronavirus pandemic, countless face-to-face events as well as medical trainings were cancelled or moved to online courses, which resulted in increased digitalization in many areas. In the context of medical education, videos provide tremendous benefit for visualizing skills before they are practised., Methods: Based on a previous investigation of video material addressing epidural catheterization available on the YouTube platform, we aimed to investigate new content produced in the context of the pandemic. Thus, a video search was conducted in May 2022., Results: We identified twelve new videos since the pandemic with a significant improvement in the new content in terms of procedural items (p = 0.03) compared to the prepandemic video content. Video content released in the course of the COVID-19 pandemic was more often created by private content creators and were significantly shorter in total runtime than those from university and medical societies (p = 0.04)., Conclusion: The profound changes in the learning and teaching of health care education in relation to the pandemic are largely unclear. We reveal improved procedural quality of predominantly privately uploaded content despite a shortened runtime compared to the prepandemic period. This might indicate that technical and financial hurdles to producing instructional videos by discipline experts have decreased. In addition to the teaching difficulties caused by the pandemic, this change is likely to be due to validated manuals on how to create such content. The awareness that medical education needs to be improved has grown, so platforms offer specialized sublevels for high-quality medical videos., (© 2023. The Author(s).)

Reperfusion injury is a very common complication of various indicated therapies such as the re-opening of vessels in the myocardium or brain as well as reflow in hemodynamic shutdown (cardiac arrest, severe trauma, aortic cross-clamping). The treatment and prevention of reperfusion injury has therefore been a topic of immense interest in terms of mechanistic understanding, the exploration of interventions in animal models and in the clinical setting in major prospective studies. While a wealth of encouraging results has been obtained in the lab, the translation into clinical success has met with mixed outcomes at best. Considering the still very high medical need, progress continues to be urgently needed. Multi-target approaches rationally linking interference with pathophysiological pathways as well as a renewed focus on aspects of microvascular dysfunction, especially on the role of microvascular leakage, are likely to provide new insights.

Background: The SARS-CoV‑2 pandemic posed unexpected challenges for hospitals worldwide and in addition to the supply emergency, simultaneously caused a high pressure to innovate. Due to the high number of cases of COVID-19 patients requiring intensive care, structured networking of hospitals gained particular importance. The tele-ICU communication platform TeleCOVID was developed to improve the quality of intensive care both by enabling teleconsultations and by supporting patient transfers., Objective: The present study aimed to survey user experiences with TeleCOVID. The study investigated the extent to which the app is used, the user experiences of the participating hospitals, and the resulting implications for the further development of the telemedicine application., Material and Methods: A user survey was conducted in May 2022 using an online questionnaire. The survey contained both closed and open questions with a free text field. It was sent via the Hessian Ministry of Social Affairs and Integration (HMSI). All 135 hospitals in Hesse were contacted by e‑mail and invited to participate in the study. The results of the closed questions were analyzed using descriptive statistics, and the results of the open questions were clustered and thematically summarized using qualitative content analysis., Results: The study showed that TeleCOVID was used primarily for transfer requests, followed by the need for a treatment consultation without a transfer request. Most often, ECMO treatment or treatment in a hospital of a higher care level was required. The content analysis showed that users particularly rated the possibility of a data protection-compliant and structured transfer of patient data as advantageous. It is also worth mentioning that in almost 25% of the cases a transfer of patients could be prevented by TeleCOVID. Disadvantages frequently mentioned by respondents were the lack of connection to the electronic hospital information system, the increased time required for the registration process, and the poor primary accessibility of contact persons., Conclusion: In a further development of the application the connection to the electronic hospital information system should be considered particularly urgent. In addition, the time expenditure should be reduced by a simplified login process. Due to interface barriers, an alternative data infrastructure would also be conceivable to create interoperability. The introduction of a web client could also increase usability. The main beneficiaries of hospital networking are physicians and patients in a context associated with a high workload and specific medical issues. Continuation and expansion of the app to intensive care medicine and beyond are therefore recommended. In further studies on the project, personal interviews with decision makers could be useful to conduct a more targeted needs analysis., (© 2023. The Author(s).)

Background: Transfusion of red blood cell concentrate can be life-saving, but requires accurate dose calculations in children., Aims: We tested the hypothesis that cognitive aids would improve identification of the correct recommended volumes and products, according to the German National Transfusion guidelines, in pediatric transfusion scenarios., Methods: Four online questionnaire-based scenarios, two with hemodynamically stable and two with hemodynamically unstable children, were sent to German and international pediatric anesthetists for completion. In the two stable scenarios, participants were given pre-filled tables that contained all required information. For the two emergency scenarios, existing algorithms were used and required calculation by the user. The results were classified into three categories of deviations from the recommended values (DRV): DRV120 (<80% or >120%), as the acceptable variation; DRV 300 (<33% or >300%), the deviation of concern for potential harm; and DRV 1000 (<10% or >1000%), the excessive deviation with a high probability of harm., Results: A total of 1.458 pediatric anesthetists accessed this simulation questionnaire, and 402 completed questionnaires were available for analysis. A pre-filled tabular aid, avoiding calculations, led to a reduction in deviation rates in the category of DRV120 by 60% for each and of DRV300 by 17% and 20%, respectively. The use of algorithms as aids for unstable emergencies led to a reduction in the deviation rate only for DRV120 (20% and 15% respectively). In contrast, the deviation rates for DRV300 and DRV1000 rose by 37% and 16%, respectively. Participants used higher transfusion thresholds for the emergency case of a 2-year-old compromised child than for the stable case with a patient of the same age (on average, 8.6 g/dL, 95% CI 8.5-8.8 versus 7.1 g/dL, 95% CI 7.0-7.2, p < 0.001) if not supported by our aids. Participants also used a higher transfusion threshold for unstable children aged 3 months than for stable children of the same age (on average, 8.9 g/dL, 95% CI 8.7-9.0 versus 7.9 g/dL, 95% CI 7.7-8.0, p < 0.001)., Conclusions: The use of cognitive aids with precalculated transfusion volumes for determining transfusion doses in children may lead to improved adherence to published recommendations, and could potentially reduce dosing deviations outside those recommended by the German national transfusion guidelines.

Patient monitoring is the foundation of intensive care medicine. High workload and information overload can impair situation awareness of staff, thus leading to loss of important information about patients' conditions. To facilitate mental processing of patient monitoring data, we developed the Visual-Patient-avatar Intensive Care Unit (ICU), a virtual patient model animated from vital signs and patient installation data. It incorporates user-centred design principles to foster situation awareness. This study investigated the avatar's effects on information transfer measured by performance, diagnostic confidence and perceived workload. This computer-based study compared Visual-Patient-avatar ICU and conventional monitor modality for the first time. We recruited 25 nurses and 25 physicians from five centres. The participants completed an equal number of scenarios in both modalities. Information transfer, as the primary outcome, was defined as correctly assessing vital signs and installations. Secondary outcomes included diagnostic confidence and perceived workload. For analysis, we used mixed models and matched odds ratios. Comparing 250 within-subject cases revealed that Visual-Patient-avatar ICU led to a higher rate of correctly assessed vital signs and installations [rate ratio (RR) 1.25; 95% CI 1.19-1.31; P < 0.001], strengthened diagnostic confidence [odds ratio (OR) 3.32; 95% CI 2.15-5.11, P < 0.001] and lowered perceived workload (coefficient - 7.62; 95% CI - 9.17 to - 6.07; P < 0.001) than conventional modality. Using Visual-Patient-avatar ICU, participants retrieved more information with higher diagnostic confidence and lower perceived workload compared to the current industry standard monitor., (© 2023. The Author(s).)

Anaemia is among the most common co-morbidity in surgical patients. However, it often remains unrecognized and untreated, which results in an increased requirement for allogeneic blood products and complications. Patient Blood Management offers patient-centred and evidence-based therapies and preventive measures for anaemia. Patient Blood Management is composed of 3 main pillars: pre-operative anaemia management, blood loss reduction and the rational use of allogeneic blood products. The World Health Organization demands the implementation of Patient Blood Management measures since 2010. However, a comprehensive implementation of Patient Blood Management as a standard-of-care is still not achieved. Here, we describe the need for a comprehensive Patient Blood Management implementation and highlight several specific Patient Blood Management measures., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose of Review: The value of healthcare is defined as the achieved health outcome in relation to the incurred costs. Patient Blood Management (PBM) is a multidisciplinary, evidence-based and patient-centred concept to optimize the patients' red blood cell mass, minimize blood loss and bleeding and to secure the physiological reserve, including the promotion of evidence-based transfusion strategies. This review describes the healthcare value and the cost effectiveness of single PBM measures as well as the implementation of comprehensive PBM programmes., Recent Findings: Overall, measures improving surgical outcome and reducing hospital length of stay, such as intravenous iron supplementation in iron deficient anaemic patients, the use of antifibrinolytic agents for the treatment of bleeding, the use of cell salvage and adherence to an evidence-based transfusion strategy, are associated with cost savings., Summary: Although several single PBM measures have been shown to be effective and cost-efficient, it remains challenging to compare the results among differing healthcare systems., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The Department of Anaesthesiology, Intensive Care Medicine & Pain Therapy of the University Hospital Frankfurt, Goethe University received support from B. Braun Melsungen, CSL Behring, Fresenius Kabi, and Vifor Pharma for the implementation of Frankfurt‘s Patient Blood Management program. KZ has received honoraria for participation in advisory board meetings for Haemonetics and Vifor and received speaker fees from CSL Behring, Masimo, Pharmacosmos, Boston Scientific, Salus, iSEP, Edwards and GE Healthcare. He is the Principal Investigator of the EU-Horizon 2020 project ENVISION (Intelligent plug-and-play digital tool for real-time surveillance of COVID-19 patients and smart decision-making in Intensive Care Units) and Horizon Europe 2021 project COVend (Biomarker and AI-supported FX06 therapy to prevent progression from mild and moderate to severe stages of COVID-19).

The level of neuromuscular blockade can be assessed by subjective (qualitative) and objective (quantitative) methods. This study aims to compare the dosage of the neuromuscular blocking agents (NMBA) rocuronium and the need for reversion by sugammadex between those methods. A retrospective, observational analysis was conducted. In the tactile qualitative-neuromuscular monitoring-group (tactile NMM) (n = 244), muscle contractions were assessed tactilely. In the quantitative neuromuscular monitoring-group (n = 295), contractions were accessed using an acceleromyograph. Primary endpoints were dosage of rocuronium per minute operation-time (milligram per kilogram bodyweight per minute (mg/kgBW/min)), count of repeated rocuronium administrations and use of sugammadex. Secondary endpoints were: NMM use before repeated NMBA application or extubation, time to extubation, post-operative oxygen demand. A total of n = 539 patients were included. n = 244 patients were examined with tactile NMM and 295 patients by quantitative NMM. Quantitative NMM use resulted in significantly lower rocuronium dosing (tactile NMM: 0.01 (± 0.007) mg/kgBW/min vs. quantitative NMM: 0.008 (± 0.006) mg/kgBW/min (p < 0.001)). In quantitative NMM use fewer repetitions of rocuronium application were necessary (tactile NMM: 83% (n = 202) vs. quantitative NMM: 71% (n = 208) p = 0.007). Overall, 24% (n = 58) in the tactile NMM-group, and 20% (n = 60) in the quantitative NMM-group received sugammadex ((p = 0.3), OR: 1.21 (0.81-1.82)). Significantly fewer patients in the quantitative NMM-group required oxygen-supply postoperative (quantitative NMM: 43% (n = 120)) vs. tactile NMM: 57% (n = 128)) (p = 0.002). The use of quantitative assessment of NMBA results in a lower overall dosage and requires fewer repetitions of rocuronium application. Therefore, quantitative monitoring systems should be used to monitor NMBA intraoperatively to reduce NMBA dosing, while achieving continuous neuromuscular blockade., (© 2022. The Author(s).)

Background: Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management., Design: A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline., Results: These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%., Discussion: Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality., Conclusion: All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) therapy has become increasingly used and established in many hospitals as a routine treatment. With ECMO-therapy being a resource-demanding procedure, it is of interest whether a more prolonged VV-ECMO treatment would hold sufficient therapeutic success. Our retrospective study included all VV-ECMO runs from 1 January 2020 to 31 June 2022. We divided all runs into four groups (<14 days, 14-27, 28-49, 50+) of different durations and looked for differences overall in hospital survival. Additionally, corresponding treatments and therapeutic modalities, as well as laboratory results, were analyzed. We included 117 patients. Of those, 97 (82.9%) received a VV-ECMO treatment longer than two weeks. We did not find a significant association between ECMO duration ( p = 0.15) and increased mortality though a significant correlation between the patients' age and their probability of survival ( p = 0.02). Notably, we found significantly lower interleukin-6 levels with an increase in therapy duration ( p < 0.01). Our findings show no association between the duration of ECMO therapy and mortality. Thus, the treatment duration alone may not be used for making assumptions about the prospect of survival. However, attention is also increasingly focused on long-term outcomes, such as post-intensive care syndrome with severe impairments.

Interpreting blood gas analysis results can be challenging for the clinician, especially in stressful situations under time pressure. To foster fast and correct interpretation of blood gas results, we developed Visual Blood. This computer-based, multicentre, noninferiority study compared Visual Blood and conventional arterial blood gas (ABG) printouts. We presented six scenarios to anaesthesiologists, once with Visual Blood and once with the conventional ABG printout. The primary outcome was ABG parameter perception. The secondary outcomes included correct clinical diagnoses, perceived diagnostic confidence, and perceived workload. To analyse the results, we used mixed models and matched odds ratios. Analysing 300 within-subject cases, we showed noninferiority of Visual Blood compared to ABG printouts concerning the rate of correctly perceived ABG parameters (rate ratio, 0.96; 95% CI, 0.92-1.00; p = 0.06). Additionally, the study revealed two times higher odds of making the correct clinical diagnosis using Visual Blood (OR, 2.16; 95% CI, 1.42-3.29; p < 0.001) than using ABG printouts. There was no or, respectively, weak evidence for a difference in diagnostic confidence (OR, 0.84; 95% CI, 0.58-1.21; p = 0.34) and perceived workload (Coefficient, 2.44; 95% CI, -0.09-4.98; p = 0.06). This study showed that participants did not perceive the ABG parameters better, but using Visual Blood resulted in more correct clinical diagnoses than using conventional ABG printouts. This suggests that Visual Blood allows for a higher level of situation awareness beyond individual parameters' perception. However, the study also highlighted the limitations of today's virtual reality headsets and Visual Blood.

Artificial intelligence (AI) is predicted to play an increasingly important role in perioperative medicine in the very near future. However, little is known about what anesthesiologists know and think about AI in this context. This is important because the successful introduction of new technologies depends on the understanding and cooperation of end users. We sought to investigate how much anesthesiologists know about AI and what they think about the introduction of AI-based technologies into the clinical setting. In order to better understand what anesthesiologists think of AI, we recruited 21 anesthesiologists from 2 university hospitals for face-to-face structured interviews. The interview transcripts were subdivided sentence-by-sentence into discrete statements, and statements were then grouped into key themes. Subsequently, a survey of closed questions based on these themes was sent to 70 anesthesiologists from 3 university hospitals for rating. In the interviews, the base level of knowledge of AI was good at 86 of 90 statements (96%), although awareness of the potential applications of AI in anesthesia was poor at only 7 of 42 statements (17%). Regarding the implementation of AI in anesthesia, statements were split roughly evenly between pros (46 of 105, 44%) and cons (59 of 105, 56%). Interviewees considered that AI could usefully be used in diverse tasks such as risk stratification, the prediction of vital sign changes, or as a treatment guide. The validity of these themes was probed in a follow-up survey of 70 anesthesiologists with a response rate of 70%, which confirmed an overall positive view of AI in this group. Anesthesiologists hold a range of opinions, both positive and negative, regarding the application of AI in their field of work. Survey-based studies do not always uncover the full breadth of nuance of opinion amongst clinicians. Engagement with specific concerns, both technical and ethical, will prove important as this technology moves from research to the clinic.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery., Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients., Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized., Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 μg/L of sodium selenite prior to cardiopulmonary bypass, 2000 μg/L immediately postoperatively, and 1000 μg/L each day in intensive care for a maximum of 10 days or placebo., Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery., Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups., Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery., Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

Acid-base homeostasis is crucial for all physiological processes in the body and is evaluated using arterial blood gas (ABG) analysis. Screens or printouts of ABG results require the interpretation of many textual elements and numbers, which may delay intuitive comprehension. To optimise the presentation of the results for the specific strengths of human perception, we developed Visual Blood, an animated virtual model of ABG results. In this study, we compared its performance with a conventional result printout. Seventy physicians from three European university hospitals participated in a computer-based simulation study. Initially, after an educational video, we tested the participants' ability to assign individual Visual Blood visualisations to their corresponding ABG parameters. As the primary outcome, we tested caregivers' ability to correctly diagnose simulated clinical ABG scenarios with Visual Blood or conventional ABG printouts. For user feedback, participants rated their agreement with statements at the end of the study. Physicians correctly assigned 90% of the individual Visual Blood visualisations. Regarding the primary outcome, the participants made the correct diagnosis 86% of the time when using Visual Blood, compared to 68% when using the conventional ABG printout. A mixed logistic regression model showed an odds ratio for correct diagnosis of 3.4 (95%CI 2.00-5.79, p < 0.001) and an odds ratio for perceived diagnostic confidence of 1.88 (95%CI 1.67-2.11, p < 0.001) in favour of Visual Blood. A linear mixed model showed a coefficient for perceived workload of -3.2 (95%CI -3.77 to -2.64) in favour of Visual Blood. Fifty-one of seventy (73%) participants agreed or strongly agreed that Visual Blood was easy to use, and fifty-five of seventy (79%) agreed that it was fun to use. In conclusion, Visual Blood improved physicians' ability to diagnose ABG results. It also increased perceived diagnostic confidence and reduced perceived workload. This study adds to the growing body of research showing that decision-support tools developed around human cognitive abilities can streamline caregivers' decision-making and may improve patient care.

Red blood cell (RBC) transfusion is a life-saving medical intervention and has an essential role in the management of surgical patients. However, blood donations and supply levels are decreasing, therefore there is an unmet need for the accurate prediction of the transfusion probability for surgical patients. Multiple methods have been established to predict the need for RBC transfusion. Maximum surgical blood order schedules are widely used in the clinical setting. However, these lists are not designed to accurately predict RBC utilization for an individual case as factors such as preoperative haemoglobin level, total body blood volume, comedications are not considered. Artificial intelligence and related technologies based on machine learning modelling are valuable alternatives to predict transfusion probability taking into account patient individual risk factors including among others comorbidities, laboratory parameters, use of oral anticoagulation, ASA score, surgeon's ID or applied blood saving measures. Overall, forecasting the need for a RBC transfusion can facilitate personalized medicine, quality assurance, decrease blood wastage, decrease costs, and increase patient safety. Furthermore, transfusion prediction models could facilitate blood management strategies before surgery., (Copyright © 2022 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Background: Every year a large number of patients is suffering from influenza infection with often severe outcome. The influenza season 2017/2018 was characterized by a high number of cases (in Germany>346,000 laboratory-confirmed cases), but also by a high rate of hospitalizations with sometimes severe clinical outcome - also in the group of patients under 60 years., Aim: The aim of the present study was to find out whether patients not fullfilling the STIKO vaccination recommendation in the 2017/18 season were suffering from a worse outcome., Materials and Methods: All laboratory-confirmed influenza patients at Frankfurt University Hospital were retrospectively analyzed for disease severity with respect to the primary endpoint. Secondary endpoints were defined as demographic data, length of hospital stay, previous illnesses, intensive care therapy and its duration, drug therapy, and mortality., Results: Fifty-one of 303 patients (16.8%) required intensive care treatments. Of these 51, 46 patients (90.2%) belonged to the group that should have been vaccinated according to the vaccination recommendations according to STIKO, 5 patients (9.8%) did not belong to this group (p=0.434). Of the 51 ICU patients, 16 (31.4%) died. All deceased were from the group with vaccination recommendation (p=0.120)., Conclusions: Based on these data, it appears that severe disease progression occurs in both the group of patients with and without STIKO vaccination recommendation, but deaths occur only in the group of patients with recommendation., Competing Interests: PD Dr. Haitham Mutlak erhielt Vortragshonorare der Firma Getinge.Prof. Dr. Sabine Wicker begleitet das Amt der stellvertretenden Vorsitzenden der STIKO. Prof. Dr. Dr. Zacharowski erhielt Beraterhonorare von Haemonetics und Vifor sowie Vortragshonorare von CSL Behring und GE Healthcare. Er ist der Studienleiter des EU-Horizon 2020 Projekts ENVISION und des Horizon Europe 2021 Projekts COVend. Alle weiteren Autoren geben an, dass kein Interessenskonflikt vorliegt., (Thieme. All rights reserved.)

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases., Competing Interests: SR, GS, LK, SQ Though unrelated to the contents of this manuscript, the authors declare that SMR, GS, LK, and SQ are co-founders of Cysmic GmbH, ML Affiliated with Cysmic GmbH; the author has no financial interests to declare, FG, MD, PM, KZ, Av, CW No competing interests declared, AD Though unrelated to the contents of this manuscript, AD is a founder of Omix Technologies Inc and Altis Biosciences LLC, and a scientific advisory board member for Hemanext Inc and Forma Therapeutics, (© 2022, Recktenwald, Simionato et al.)

BACKGROUNDResults of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODSOf 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group.RESULTSThe median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups.CONCLUSIONThe trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19.Trial registrationEudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health).

Background: Primary viral myocarditis associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection is a rare diagnosis., Case Presentation: We report the case of an unvaccinated, healthy patient with cardiogenic shock in the context of a COVID-19-associated myocarditis and therapy with simultaneous veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and percutaneous left ventricular decompression therapy with an Impella. The aim of this review is to provide an overview of therapeutic options for patients with COVID-19-associated myocarditis., Conclusions: The majority of patients required a combination of two assist devices to achieve sufficient cardiac output until recovery of left ventricular ejection fraction. Due to the rapid onset of this fulminant cardiogenic shock immediate invasive bridging therapy in a specialized center was lifesaving., (© 2022. The Author(s).)

Abstract: Background: Severe progression of coronavirus disease 2019 (COVID-19) causes respiratory failure and critical illness. Recently, COVID-19 has been associated with heparanase (HPSE)-induced endothelial barrier dysfunction and inflammation, so called endothelitis, and therapeutic treatment with heparin or low-molecular-weight heparin (LMWH) targeting HPSE has been postulated. Because, up to this date, clinicians are unable to measure the severity of endothelitis, which can lead to multiorgan failure and concomitant death, we investigated plasma levels of HPSE and heparin-binding protein (HBP) in COVID-19 intensive care patients to render a possible link between endothelitis and these plasma parameters. Therefore, a prospective prolonged cohort study was conducted, including 47 COVID-19 patients from the intensive care unit. Plasma levels of HPSE, and HBP were measured daily by enzyme-linked immunosorbent assay in survivors (n = 35) and nonsurvivors (n = 12) of COVID-19 from admission until discharge or death. All patients were either treated with heparin or LMWH, aiming for an activated partial thromboplastin time of ≥60 seconds or an anti-Xa level of >0.8 IU/mL using enoxaparin, depending on the clinical status of the patient (patients with extracorporeal membrane oxygenation or >0.1 μg/kg/min noradrenaline received heparin, all others enoxaparin). Results: We found significantly higher plasma levels of HPSE and HBP in survivors and nonsurvivors of COVID-19, compared with healthy controls. Still, interestingly, plasma HPSE levels were significantly higher ( P < 0.001) in survivors compared with nonsurvivors of COVID-19. In contrast, plasma HBP levels were significantly reduced ( P < 0.001) in survivors compared with nonsurvivors of COVID-19. Furthermore, when patients received heparin, they had significantly lower HPSE ( P = 2.22 e - 16) and significantly higher HBP ( P = 0.00013) plasma levels as when they received LMWH. Conclusion: Our results demonstrated that patients, who recover from COVID-19-induced vascular and pulmonary damage and were discharged from the intensive care unit, have significantly higher plasma HPSE level than patients who succumb to COVID-19. Therefore, HPSE is not suitable as marker for disease severity in COVID-19 but maybe as marker for patient's recovery. In addition, patients receiving therapeutic heparin treatment displayed significantly lower heparanse plasma level than upon therapeutic treatment with LMWH., Competing Interests: The Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy of the University Hospital Frankfurt received support from B. Braun Melsungen, CSL Behring, Fresenius Kabi, and Vifor Pharma for the implementation of Frankfurt's Patient Blood Management program, and KZ received honoraria for scientific lectures and ad board meeting within the last 3 years from CSL Behring, GE Healthcare, Edwards, Haemonetics, implatcast GmbH, med Update GmbH, Pharmacosmos, and Vifor Pharma. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 by the Shock Society.)

Purpose of Review: The particular fields within patient blood management (PBM) and patient safety reviewed here include novel insights into bleeding therapy, autologous cell salvage, and perioperative anemia therapy., Recent Finding: World Health Organization has published that implementation of PBM is important but has not yet been performed in all hospitals. Two antibodies that mimic the function of FVIII, Emicizumab, and Mim8 have been developed. Tranexamic acid (TXA) has been investigated further in patients with hip surgery and shows reduction of bleeding. Thrombocytopenia in patients undergoing cardiac surgery is a particular concern that has been investigated in another trial. The use of autologous cell salvage was updated in form of a review and meta-analysis. And last but not least, intravenous iron in preoperative anemia therapy can reduce the number of transfusions, but especially iron carboxymaltose can cause hypophosphatemia., Summary: PBM should be further implemented in more hospitals. Emicizumab and Mim8 are indicated in acquired hemophilia or hemophilia A with inhibitors. TXA was confirmed to reduce bleeding. Autologous cell salvage is state of the art to reduce transfusion requirements in major cardiac and noncardiac surgery. Serum phosphate concentrations should be monitored after administration of intravenous iron compounds., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intraoperative hypotension is common in patients having non-cardiac surgery and is associated with serious complications and death. However, optimal intraoperative blood pressures for individual patients remain unknown. We therefore aim to test the hypothesis that personalized perioperative blood pressure management-based on preoperative automated blood pressure monitoring-reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery., Methods: IMPROVE-multi is a multicenter randomized trial in 1272 high-risk patients having elective major abdominal surgery that we plan to conduct at 16 German university medical centers. Preoperative automated blood pressure monitoring using upper arm cuff oscillometry will be performed in all patients for one night to obtain the mean of the nighttime mean arterial pressures. Patients will then be randomized either to personalized blood pressure management or to routine blood pressure management. In patients assigned to personalized management, intraoperative mean arterial pressure will be maintained at least at the mean of the nighttime mean arterial pressures. In patients assigned to routine management, intraoperative blood pressure will be managed per routine. The primary outcome will be a composite of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery., Discussion: Our trial will determine whether personalized perioperative blood pressure management reduces the incidence of major postoperative complications and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery., Trial Registration: ClinicalTrials.gov NCT05416944. Registered on June 14, 2022., (© 2022. The Author(s).)

Background: Blood transfusions are common medical procedures and every age group requires detailed insights and treatment bundles. The aim of this study was to examine the association of anaemia, co-morbidities, complications, in-hospital mortality, and transfusion according to age groups to identify patient groups who are particularly at risk when undergoing surgery., Methods: Data from 21 Hospitals of the Patient Blood Management Network Registry were analysed. Patients were divided into age subgroups. The incidence of preoperative anaemia, co-morbidities, surgical disciplines, hospital length of stay, complications, in-hospital mortality rate, and transfusions were analysed by descriptive and multivariate regression analysis., Results: A total of 1 117 919 patients aged 18-108 years were included. With increasing age, the number of co-morbidities and incidence of preoperative anaemia increased. Complications, hospital length of stay, and in-hospital mortality increased with age and were higher in patients with preoperative anaemia. The mean number of transfused red blood cells (RBCs) peaked, whereas the transfusion rate increased continuously. Multivariate regression analysis showed that increasing age, co-morbidities, and preoperative anaemia were independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion., Conclusion: Increasing age, co-morbidities, and preoperative anaemia are independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. Anaemia diagnosis and treatment should be established in all patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Anaemia is a risk factor for several adverse postoperative outcomes. Detailed data about the prevalence of anaemia are not available over a long time-period in Germany. In this retrospective, observational, multicentre study, patients undergoing surgery in March in 2007, 2012, 2015, 2017 and 2019 were studied. The primary objective was the prevalence of anaemia at hospital admission. The secondary objectives were the association between anaemia and the number of units of red blood cells transfused, length of hospital stay and in-hospital mortality. A total of 23,836 patients were included from eight centres. The prevalence of pre-operative anaemia in patients aged ≥ 18 years decreased slightly from 37% in 2007 to 32.5% in 2019 (p = 0.01) and increased in patients aged ≤ 18 years from 18.8% in 2007 to 26.4% in 2019 (p > 0.001). The total amount of blood administered per 1000 patients decreased from 671.2 units in 2007 to 289.0 units in 2019. Transfusion rates in anaemic patients declined from 33.8% in 2007 to 19.1% in 2019 (p < 0.001) and in non-anaemic patients from 8.4% in 2007 to 3.4% in 2019 (p < 0.001). Overall, the mortality rate remained constant over the years: 2.9% in 2007, 2.1% in 2012, 2.5% in 2015, 1.9% in 2017 and 2.5% in 2019. In the presence of anaemia, mortality was significantly increased compared with patients without anaemia (OR 5.27 (95%CI 4.13-6.77); p < 0.001). Red blood cell transfusion was associated with an increased risk of mortality (OR 14.98 (95%CI 11.83-19.03); p < 0.001). Using multivariable linear regression analysis with fixed effects, we found that pre-operative anaemia (OR 2.08 (95%CI 1.42-3.05); p < 0.001) and red blood cell transfusion (OR 4.29 (95%CI 3.09-5.94); p < 0.001) were predictors of mortality but not length of stay (0.99 (95%CI 0.98-1.00) days; p = 0.12) and analysed years (2007 vs. 2019: OR 1.49 (95%CI 0.86-2.69); p = 0.07). Pre-operative anaemia affects more than 30% of surgical patients in Germany and multidisciplinary action is urgently required to reduce adverse outcomes., (© 2022 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Objectives: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP)., Methods: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models., Results: The majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models., Conclusion: This analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Körper, Schrezenmeier, Rincon-Arevalo, Grüner, Zickler, Weiss, Wiesmann, Zacharowski, Kalbhenn, Bentz, Dollinger, Paul, Lepper, Ernst, Wulf, Zinn, Appl, Jahrsdörfer, Rojewski, Lotfi, Dörner, Jungwirth, Seifried, Fürst and Schrezenmeier.)

Following elective craniotomy, patients routinely receive 24-h monitoring in an intensive care unit (ICU). However, the benefit of intensive care monitoring and treatment in these patients is discussed controversially. This study aimed to evaluate the complication profile of a "No ICU - Unless" strategy and to compare this strategy with the standardized management of post-craniotomy patients in the ICU. Two postoperative management strategies were compared in a matched-pair analysis: The first cohort included patients who were managed in the normal ward postoperatively ("No ICU - Unless" group). The second cohort contained patients routinely admitted to the ICU (control group). Outcome parameters contained detailed complication profile, length of hospital and ICU stay, duration to first postoperative mobilization, number of unplanned imaging before scheduled postoperative imaging, number and type of intensive care interventions, as well as pre- and postoperative modified Rankin scale (mRS). Patient characteristics and clinical course were analyzed using electronic medical records. The No ICU - Unless (NIU) group consisted of 96 patients, and the control group consisted of 75 patients. Complication rates were comparable in both cohorts (16% in the NIU group vs. 17% in the control group; p = 0.123). Groups did not differ significantly in any of the outcome parameters examined. The length of hospital stay was shorter in the NIU group but did not reach statistical significance (average 5.8 vs. 6.8 days; p = 0.481). There was no significant change in the distribution of preoperative (p = 0.960) and postoperative (p = 0.425) mRS scores in the NIU and control groups. Routine postoperative ICU management does not reduce postoperative complications and does not affect the surgical outcome of patients after elective craniotomies. Most postoperative complications are detected after a 24-h observation period. This approach may represent a potential strategy to prevent the overutilization of ICU capacities while maintaining sufficient postoperative care for neurosurgical patients., (© 2022. The Author(s).)

Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear. In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77-177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals. At follow-up (329 days (IQR, 274-383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness., (© 2022. The Author(s).)

Background: Anaesthesiology represents a rapidly evolving medical specialty in global healthcare, currently covering advanced peri-operative, pre-hospital and in-hospital critical emergency management (CREM), intensive care medicine (ICM) and pain management. The aim of the European Society of Anaesthesiology and Intensive Care (ESAIC) is to develop and promote a coordinated interdisciplinary and multidisciplinary European network of Anaesthesiology and Intensive Care Medicine (AICM) societies for improvement of patient safety and outcome, and to enhance political and public awareness of the role of anaesthesiologists all over Europe. The ESAIC promotes coordinated interdisciplinary and multidisciplinary care for severely compromised patients, based on the European training requirements (ETR) within the European Union of Medical Specialists (UEMS)., Methods: To define the current situation of AICM in Europe, a survey was sent in April 2019 to the ESAIC Council and the ESAIC National Anaesthesiologists Societies Committee (NASC) members. The survey posed questions regarding the year of foundation, the inclusion of ICM in the society name, and if, and to what extent, various kinds (postoperative, general, specific, mixed) of national ICUs are being run by differing medical specialties. The study data were compiled and analysed by the ESAIC Board, Council and NASC in December 2019., Results and Conclusion: Amongst the 42 European national societies surveyed (41 members of ESAIC-NASC plus Luxembourg), nineteen (45%) also include terms related to critical care medicine or ICM in their names, seven (17%) include terms related to reanimation and three (7%) to resuscitation. In recent years, several national societies revised their names to better reflect their gradual embrace of peri-operative medicine, ICM, CREM and pain management. Approximately 70% of ICU beds in Europe, and 100% in Scandinavia, are being run by anaesthesiologists, the remaining 30% being managed by physicians from other surgical or medical specialties. To emphasise future needs and resources of European AICM, the ESAIC drafted an ICM roadmap in terms of clinical practice, organisation of healthcare, interprofessional and interdisciplinary collaboration, patient safety, outcome and empowerment, professional working conditions, and changes in research, teaching and training required to meet future challenges and expectations., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology.)

COVID-19 adds to the complexity of optimal timing for tracheostomy. Over the course of this pandemic, and expanded knowledge of the disease, many centers have changed their operating procedures and performed an early tracheostomy. We studied the data on early and delayed tracheostomy regarding patient outcome such as mortality. We performed a retrospective analysis of all tracheostomies at our institution in patients diagnosed with COVID-19 from March 2020 to June 2021. Time from intubation to tracheostomy and mortality of early (≤ 10 days) vs. late (&gt; 10 days) tracheostomy were the primary objectives of this study. We used mixed cox-regression models to calculate the effect of distinct variables on events. We studied 117 tracheostomies. Intubation to tracheostomy shortened significantly (Spearman's correlation coefficient; rho = - 0.44, p ≤ 0.001) during the course of this pandemic. Early tracheostomy was associated with a significant increase in mortality in uni- and multivariate analysis (Hazard ratio 1.83, 95% CI 1.07-3.17, p = 0.029). The timing of tracheostomy in COVID-19 patients has a potentially critical impact on mortality. The timing of tracheostomy has changed during this pandemic tending to be performed earlier. Future prospective research is necessary to substantiate these results., (© 2022. The Author(s).)

Purpose: Early accurate diagnosis of infection ± organ dysfunction (sepsis) remains a major challenge in clinical practice. Utilizing effective biomarkers to identify infection and impending organ dysfunction before the onset of clinical signs and symptoms would enable earlier investigation and intervention. To our knowledge, no prior study has specifically examined the possibility of pre-symptomatic detection of sepsis., Methods: Blood samples and clinical/laboratory data were collected daily from 4385 patients undergoing elective surgery. An adjudication panel identified 154 patients with definite postoperative infection, of whom 98 developed sepsis. Transcriptomic profiling and subsequent RT-qPCR were undertaken on sequential blood samples taken postoperatively from these patients in the three days prior to the onset of symptoms. Comparison was made against postoperative day-, age-, sex- and procedure- matched patients who had an uncomplicated recovery (n =151) or postoperative inflammation without infection (n =148)., Results: Specific gene signatures optimized to predict infection or sepsis in the three days prior to clinical presentation were identified in initial discovery cohorts. Subsequent classification using machine learning with cross-validation with separate patient cohorts and their matched controls gave high Area Under the Receiver Operator Curve (AUC) values. These allowed discrimination of infection from uncomplicated recovery (AUC 0.871), infectious from non-infectious systemic inflammation (0.897), sepsis from other postoperative presentations (0.843), and sepsis from uncomplicated infection (0.703)., Conclusion: Host biomarker signatures may be able to identify postoperative infection or sepsis up to three days in advance of clinical recognition. If validated in future studies, these signatures offer potential diagnostic utility for postoperative management of deteriorating or high-risk surgical patients and, potentially, other patient populations., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Objective: We explored the feasibility of a Clinical Decision Support System (CDSS) to guide evidence-based perioperative anticoagulation., Design: Prospective randomised clinical management simulation multicentre study., Setting: Five University and 11 general hospitals in Germany., Participants: We enrolled physicians (anaesthesiologist (n = 73), trauma surgeons (n = 2), unknown (n = 1)) with different professional experience., Interventions: A CDSS based on a multiple-choice test was developed and validated at the University Hospital of Frankfurt (phase-I). The CDSS comprised European guidelines for the management of anticoagulation in cardiology, cardio-thoracic, non-cardio-thoracic surgery and anaesthesiology. Phase-II compared the efficiency of physicians in identifying evidence-based approach of managing perioperative anticoagulation. In total 168 physicians were randomised to CDSS (PERI-KOAG) or CONTROL., Measurements: Overall mean score and association of processing time and professional experience were analysed. The multiple-choice test consists of 11 cases and two correct answers per question were required to gain 100% success rate (=22 points)., Main Results: In total 76 physicians completed the questionnaire (n = 42 PERI-KOAG; n = 34 CONTROL; attrition rate 54%). Overall mean score (max. 100% = 22 points) was significantly higher in PERI-KOAG compared to CONTROL (82 ± 15% vs. 70 ± 10%; 18 ± 3 vs. 15 ± 2 points; P = 0.0003). A longer processing time is associated with significantly increased overall mean scores in PERI-KOAG (≥33 min. 89 ± 10% (20 ± 2 points) vs. <33 min. 73 ± 15% (16 ± 3 points), P = 0.0005) but not in CONTROL (≥33 min. 74 ± 13% (16 ± 3 points) vs. <33 min. 69 ± 9% (15 ± 2 points), P = 0.11). Within PERI-KOAG, there is a tendency towards higher results within the more experienced group (>5 years), but no significant difference to less (≤5 years) experienced colleagues (87 ± 10% (19 ± 2 points) vs. 78 ± 17% (17 ± 4 points), P = 0.08). However, an association between professional experience and success rate in CONTROL has not been shown (71 ± 8% vs. 70 ± 13%, 16 ± 2 vs. 15 ± 3 points; P = 0.66)., Conclusions: CDSS significantly improved the identification of evidence-based treatment approaches. A precise usage of CDSS is mandatory to maximise efficiency., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients., Methods: IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (≥ 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4-6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 × 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability., Discussion: With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for., Trial Registration: EudraCT 2021-005059-35 . Registered on 12 December 2021. Study Code TMP-2204-2021-47., (© 2022. The Author(s).)

The biomedical consequences of allogeneic blood transfusions and the possible pathomechanisms of transfusion-related morbidity and mortality are still not entirely understood. In retrospective studies, allogeneic transfusion was associated with increased rates of cancer recurrence, metastasis and death in patients with colorectal cancer. However, correlation does not imply causation. The purpose of this study was to elucidate this empirical observation further in order to address insecurity among patients and clinicians. We focused on the in vitro effect of microparticles derived from red blood cell units (RMPs). We incubated different colon carcinoma cells with RMPs and analyzed their effects on growth, invasion, migration and tumor marker expression. Furthermore, effects on Wnt, Akt and ERK signaling were explored. Our results show RMPs do not seem to affect functional and phenotypic characteristics of different colon carcinoma cells and did not induce or inhibit Wnt, Akt or ERK signaling, albeit in cell culture models lacking tumor microenvironment. Allogeneic blood transfusions are associated with poor prognosis, but RMPs do not seem to convey tumor-enhancing effects. Most likely, the circumstances that necessitate the transfusion, such as preoperative anemia, tumor stage, perioperative blood loss and extension of surgery, take center stage.

Purpose: Anaemia is one of the leading causes of death among severely injured patients. It is also known to increase the risk of death and prolong the length of hospital stay in various surgical groups. The main objective of this study is to analyse the anaemia rate on admission to the emergency department and the impact of anaemia on in-hospital mortality., Methods: Data from the TraumaRegister DGU ® (TR-DGU) between 2015 and 2019 were analysed. Inclusion criteria were age ≥ 16 years and most severe Abbreviated Injury Scale (AIS) score ≥ 3. Patients were divided into three anaemia subgroups: no or mild anaemia (NA), moderate anaemia (MA) and severe anaemia (SA). Pre-hospital data, patient characteristics, treatment in the emergency room (ER), outcomes, and differences between trauma centres were analysed., Results: Of 67,595 patients analysed, 94.9% (n = 64,153) exhibited no or mild anaemia (Hb ≥ 9 g/dl), 3.7% (n = 2478) displayed moderate anaemia (Hb 7-8 g/dl) and 1.4% (n = 964) presented with severe anaemia (Hb < 7 g/dl). Haemoglobin (Hb) values ranged from 3 to 18 g/dl with a mean Hb value of 12.7 g/dl. In surviving patients, anaemia was associated with prolonged length of stay (LOS). Multivariate logistic regression analyses revealed moderate (p < 0.001 OR 1.88 (1.66-2.13)) and severe anaemia (p < 0.001 OR 4.21 (3.46-5.12)) to be an independent predictor for mortality. Further significant predictors are ISS score per point (OR 1.0), age 70-79 (OR 4.8), age > 80 (OR 12.0), severe pre-existing conditions (ASA 3/4) (OR 2.26), severe head injury (AIS 5/6) (OR 4.8), penetrating trauma (OR 1.8), unconsciousness (OR 4.8), shock (OR 2.2) and pre-hospital intubation (OR 1.6)., Conclusion: The majority of severely injured patients are admitted without anaemia to the ER. Injury-associated moderate and severe anaemia is an independent predictor of mortality in severely injured patients., (© 2022. The Author(s).)