Rationale: Early detection, standardized therapy, adequate infrastructure, and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute-care hospitals. Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals. This included the use of sepsis definitions, the implementation of sepsis guideline recommendations, diagnostic and therapeutic infrastructure, antibiotic stewardship, and quality improvement initiatives (QIIs) in hospitals. Measurements and Main Results: A total of 1,023 hospitals in 69 countries were included. Most of them, 835 (81.6%), were in Europe. Sepsis screening was used in 54.2% of emergency departments (EDs), 47.9% of wards, and 61.7% of ICUs. Sepsis management was standardized in 57.3% of EDs, 45.2% of wards, and 70.7% of ICUs. The implementation of comprehensive QIIs was associated with increased screening (EDs, +33.3%; wards, +44.4%; ICUs, +23.8% absolute difference) and increased standardized sepsis management (EDs, +33.6%; wards, +40.0%; ICUs, +17.7% absolute difference) compared with hospitals without QIIs. A total of 9.8% of hospitals had implemented ongoing QIIs, and 4.6% had invested in sepsis programs. Conclusions: The findings indicate that there is considerable room for improvement in a large number of mainly European hospitals, particularly with regard to early identification and standardized management of sepsis, the availability of guidelines, diagnostic and therapeutic infrastructure, and the implementation of QIIs. Further efforts are required to implement a more comprehensive and appropriate quality of care.

Background:Blood cultures (BCs) are key diagnostic elements for sepsis patients. Accurate preanalytical procedures are substantial, and results should be available as soon as possible to guide adequate antimicrobial treatment. This study aimed to evaluate BC collection practices and diagnostic capacity across European hospitals. Methods:This cross-sectional survey investigated BC diagnostics in acute care hospitals across 37 European countries in the years 2021 and 2022. Analyses included BC guidelines, collection sites, number of BC sets in emergency departments (EDs), wards, and intensive care units (ICUs). We also examined transfer after collection, the use of on-site vs. external laboratories, opening hours, rapid testing capacity, and turn-around times of BCs processed in microbiology laboratories with different infrastructures. Findings:Responses were collected from 907 hospitals in Europe. BC guidelines were available in 84·4% (741/878) of the hospitals. BCs were preferably collected by multiple-site sampling in EDs (62·7%, 461/735), in wards (64·0%, 513/802) and ICUs (68·5%, 518/756). One BC set was preferred in EDs in 38·4% (270/704), in wards in 40·5% (314/775), and ICUs in 34·9% (261/748). Two BC sets were preferred in EDs in 31·0% (218/704), in wards in 28·1% (218/775), and ICUs in 39·2% (293/748). 48·0% (402/838) of hospitals used on-site and 52·0% (436/838) external microbiology laboratories. Around-the-clock microbiological services were available in 10⋅0% (91/907), and rapid pathogen identification in 43·7% (396/907) of hospitals. Infrastructure with around-the-clock microbiological service and rapid testing was available in 7·4% (62/840) of hospitals, and probability of a final microbiological result within two days was highest in these hospitals compared to hospitals with limited microbiology service (for BC collected on wards: 19·6% vs. 52·7%, Odds Ratio 4·59 [95% CI 2·50-7·79], p < 0·0001). Interpretation:Despite the availability of BC guidelines in many hospitals, current recommendations for BC collection were often neglected. Rapid testing capacity was limited in most microbiological laboratories, and around-the-clock service for BCs was very rare. As delay in results may have a detrimental impact on patient outcomes, strategies to improve these processes are urgently needed. Funding:The European Sepsis Alliance and a grant by Becton and Dickinson.

Sepsis represents a significant healthcare challenge in Belgium with an estimated 40,952 cases annually (95% CI 31,938-54,451). This life-threatening condition leads to approximately 7,675 premature deaths per year (95% CI 6,421-9,089) and a loss of 38,106 quality-adjusted life years. The economic impact is substantial with annual costs ranging from €277 million to €4.3 billion. Despite this impact, Belgium lacks a national sepsis plan until present date. Following requests from diverse professional and patient organizations yielding public and political attention, the federal minister of Health requested a scientific advice to be written (November 2023-May 2024), as a basis for a national sepsis plan. This article describes Belgium's approach to developing a National Sepsis Action Plan, highlighting evidence-based and contextualized key recommendations aimed at reducing the sepsis burden by building on existing initiatives. A multidisciplinary working group was established, including representatives of healthcare workers and professional societies representing relevant disciplines in first, second and tertiary health care settings, home care and long-term care facilities. In addition, input was sought from public health actors and experts (e.g., surveillance, vaccination programs) and patient organizations. A Haddon matrix was made and seven key topics were specified: (1) awareness, (2) prevention, (3) early warning, (4) patient management, (5) post-sepsis rehabilitation, (6) advanced care planning and (7) surveillance and research. For each item, core group members were defined. Each group conducted literature reviews and developed recommendations tailored to the Belgian healthcare system, with consensus achieved during plenary sessions. The final document was externally reviewed by national and international experts. This is the first document addressing comprehensively sepsis prevention and care in Belgium, in its diverse presentations across the community and healthcare system. The next critical steps will involve the establishment of an implementation team and design of a detailed implementation plan.

Background: In the Resolution 70.7 in 2017, the World Health Assembly urged member states to integrate sepsis in their national health systems. In May 2022, the G7 Health Ministers reiterated the necessity to implement such resolution focusing on early detection, diagnosis, and therapy. Defining and implementing standards and established guidelines, infrastructure, laboratory capacity, and strategies should be fundamental elements of any sepsis plan. Up to now, no data exist describing the current state of care, the availability of diagnostics or the provision of training in sepsis within hospitals.Methods: A harmonised multidisciplinary cross-sectional questionnaire was used to explore sepsis care in acute care hospitals in Europe and worldwide. Eleven main indicators representing sepsis care in emergency departments, general wards, intensive care units (ICUs) and hospitals in general were assessed.Findings: Participants from 1087 hospitals in 73 countries took part. Measures for early recognition of sepsis were available in 61·9% (530/856) of the ICUs, 54·5% (429/787) of emergency departments and 47·8% (420/878) of the wards. Sepsis protocols or sepsis bundles were applied in 70·7% (597/845) of ICUs, 57·6% (452/785) of emergency departments and 45·5% (391/860) of the wards. 24-hour microbiological service providing 24/7 blood culture incubation, pathogen identification and communication of results, was available in 10·1% (106/1046), antibiotic stewardship programs existed in 68·3% (678/992) and quality improvement programs or sepsis training were provided in 31·3·% (272/868) of the hospitals.Interpretation: This study reports structures and measures of sepsis care in hospitals in Europe and worldwide for the first time. Although the results are not generalisable, this exploratory sample represents 609,650 curative care beds and, including almost a quarter of the total curative care bed capacity of the European Union and revealed significant room for improvement of sepsis care, availability of diagnostics and implementation of quality improvement programs.Trial Registration: Registered at ClinicalTrials.gov (Identifier: NCT05059808).Funding: The European Sepsis Care Survey was funded by the European Sepsis Alliance and an educational grant by Becton Dickinson S.A. (BD).Declaration of Interest: Christian S. Scheer discloses funding from European Sepsis Alliance for conducting the European Sepsis Care Survey and funding from Becton and Dickinson for technical realisation of the project. Evangelos J. Giamarellos-Bourboulis discloses grants, contracts and payment to the Hellenic Institute for the Study of Sepsis and National and Kapodistrian University of Athens from Abbott Products Operations, bioMérieux Inc, Johnson & Johnson, MSD, Sobi AB, AbbVie, InflaRx GmbH, Johnson & Johnson, Novartis, UCB Horizon 2020 grant ImmunoSep, Horizon Health Grant EPIC- CROWN-2 and RISKinCOVID; consulting fees with payment done to the National and Kapodistrian University of Athens from GSK, InflaRx GmbH, UCB, Sobi AB; Payment for lectures and presentation done to the National and Kapodistrian University of Athens from Abbott Products Operations AG, bioMérieux, Sobi AB. He is chairman of the European Sepsis Alliance (ESA). Ricard Ferrer has nothing to disclose. Evgeny A. Idelevich discloses a Institutional grant “Accelerated detection of antibiotic-resistant pathogens with epidemic potential (LAB-in-MOTION) - Determination, optimisation, and validation of test conditions for rapid tests to detect antibiotic-resistant pathogens from the German Federal Ministry of Education and Research (BMBF); An institutional grant “Rapid and sensitive detection of bacteria and fungi by direct microscopy.” from MetaSystems Hard & Software GmbH; An institutional grant “MALDI Biotyper Sirius IVD System – Project: Innovative Matrix-Assisted Laser Desorption Ionization - Time of Flight (MALDI-TOF) Mass Spectrometry Application Extensions” from the Federal state Mecklenburg-Western Pomerania through the European Regional Development Fund (ERDF); An institutional grant “MASTeR-test - Development of universal rapid tests for phenotypic antimicrobial resistance determination in microorganisms based on Matrix- Assisted Laser Desorption Ionization - Time of Flight Mass Spectrometry (MALDI-TOF MS) - Determination, optimization, and validation of test components and parameters from the German Federal Ministry of Education and Research (BMBF); Inventor remuneration for patent licenses - 3 patent applications licensed from the University of Münster to Bruker.; Consulting fees for Expert role in the quality assurance procedure for the diagnosis, treatment, and follow-up care of sepsis from Institute for Quality Assurance and Transparency in Health Care (IQTIG); Honorarium for the educational lecture “Acceleration of microbiological diagnostics of sepsis” at the 8th paediatric workshop from MSD; Chair of the symposiums at ECCMID 2022 organised by Bruker (support for congress travel). Djillali Annane has nothing to disclose. Antonio Artigas discloses a BIOVAP-2 PSP study grant from Abionic; a Septibell study grant from Loop-Dx; Consulting fees from Grifols for Evaluation Albus awards, Fabentech for Scientific advisor of EPIC-CROWN-2 project, Lilly Foundation for Scientific Advisor committee, Aerogen for Spanish Advisory meeting; Board participation ImmuneSep (DSMB Committee), Apeptico (DSMB Committee), Exvastat (Scientific Advisor Board). Abdullah Tarik Aslan has nothing to disclose. Ruslan Baltaga has nothing to disclose. Gabriella Bottari discloses Coordination for spreading the survey to pediatric hospital and PICUs across Europe as deputy chair of the infection systemic inflammation and sepsis section of the European Society of Pediatric and Neonatal Intensive Care without any payment. Hjalmar R. Bouma discloses a Research grant to his institution from Becton Dickinson, Inflammatix, Levels Diagnostics; He is unpaid board member of Dutch SepsisNet society (non- profit organization). Vladimir Černý discloses honoraria for lectures from Octapharma and Astra Zeneca; He is unpaid president of the Czech Society of Anesthesiology and Intensive Care Renata Curić Radivojević has nothing to disclose. Ken Dewitte has nothing to disclose. Mohamed Elbahnasawy has nothing to disclose. Matthias Gründling discloses a grant from the German Federal Ministry of Health to the SepsisDialog / University of Greifswald for #DeutschlandErkenntSepsis; Payment, honoraria for lectures from Becton Dickinson and bioMerieux to SepsisDialog / University of Greifswald. He is board member of Deutschland Erkennt Sepsis. Mohan Gurjar discloses receiving royalties for the Edited Books (‘Manual of ICU Procedures’ and ‘Textbook of Ventilation Fluids, Electrolytes and Blood Gases’) from the publisher Jaypee Brothers Medical Publishers (Pvt.) Ltd., New Delhi; He received financial support from the institute to attend the Annual Conferences of Indian Society of Critical Care Medicine; He was unpaid Executive committee member of the Indian Society of Critical Care Medicine (ISCCM) for the duration 2020-2022. Johanna Hästbacka discloses consulting fees from Braun; Lecturer honoraria for a Sepsis- related webinar in May 2023 from Duodecim; She is Advisory board member Paion; She is founder an unpaid chairperson of the Finnish sepsis society; Stock options Orion Pharma. Said Laribi discloses consulting fees from BRAHMS. Annmarie Lassen discloses a grant from Novo Nordish Foundation to her institution, consulting fees and support for meetings and travel from Odense University Medicine. Konstantin Lebedinskii has nothing to disclose. Jan Máca has nothing to disclose. Manu L.N.G. Malbrain discloses consulting fees from BBraun, Becton Dickinson, ConvaTec, Spiegelberg; Speakers Fee from PeerVoice and Cytosorbents; Meeting and travel support from MedCaptain; A European Patent on CiMON probe and GEF/GEDVI Pulsion Medical systems; He is member of the medical advisory board Getinge group, Serenno, Medical, Potrero Medical, Sentinel Medical and Baxter, CMO Medaman, Senior advisor LynxCare; He is president of the International Fluid Academy and Treasurer Abdominal Compartment Society; Stock options Serenno Medical and Potrero Medical Gianpaola Monti discloses honoraria for lectures from MD, PFIZER and GETINGE; She is communication referent of SIAART (Italian Society of Anaesthesia and Intensive Care Medicine) Marlies Ostermann has nothing to disclose. Michael Osthoff discloses grants from Swiss National Science Foundation and Botnar Research Center for Child Health to his institution; Consulting fees from Pharming Biotechnologies B.V. paid to his institution and support to attend ECCMID 2023 from Tillots Pharma. José Artur Paiva discloses consulting fees from MSD, Pfizer, Gilead, AOP and honoraria for lectures from MSD, Pfizer, Gilead, Cepheid Michela Sabbatucci discloses National coordination for spreading the call for participation in 19 regions and 2 autonomous provinces in Italy in this study with any payment neither for myself nor for the participating centres/hospitals/patients. Jakub Śmiechowicz discloses consulting fees from Alteco Medical AB and honoraria for lectures from Radiometer and Alteco Medical AB. Mihai Gabriel Ştefan discloses honoraria for lectures from Vifor Pharma, Takeda Pharmaceuticals and AstraZeneca; He is Advisory board member Livanova and unpaid Board member of the Romanian Society of Anaesthesia and Intensive Care. Marcus Vollmer has nothing to disclose. Natalija Vukovic has nothing to disclose. Kyriakos Zaragkoulias discloses national coordination to disseminate the call for participation in this study. I ensure that neither I nor the participating centers/hospitals/patients have received any payment. Konrad Reinhart discloses holding shares from InflaRx NV, which is based in Jena, Germany and listed at NASDQ, this company recently received emergency use authorization by the FDA for an antibody against C5a. Gohibic (vilobelimab) – to treat critically ill COVID-19 patients, which fulfill the criteria for viral sepsis. He is the Founding President of the Global Sepsis Alliance. Adam Linder has nothing to disclose. Daniela Filipescu is Deputy chair of the European Sepsis Alliance (ESA) and representative of the European Society of Anaesthesiology and Intensive Care (ESAIC) to the ESA, both unpaid.Ethical Approval: The study received ethical approval (BB 124/21) from the ethics committee of the University Medicine Greifswald, Germany.

BACKGROUND AND IMPORTANCE:Different triage systems can be used to screen for sepsis and are often incorporated into local electronic health records. Often the design and interface of these digitalizations are not audited, possibly leading to deleterious effects on screening test performance.OBJECTIVE:To audit a digital version of the MTS for detection of sepsis during triage in the ED.DESIGN:A single-center retrospective study SETTINGS AND PARTICIPANTS: Patients (n=29766) presenting to an ED of a tertiary-care center who received formal triage were included.OUTCOME MEASURES AND ANALYSIS:Calculated performance measures included sensitivity, specificity, likelihood ratios, and AUC for the detection of sepsis. Errors in the application of the specific sepsis discriminator of the MTS were recorded.MAIN RESULTS:A total of 189 (0.7%) subjects met the Sepsis-3 criteria, with 47 cases meeting the criteria for septic shock. The MTS had a low sensitivity of 47.6% (95% CI 40.3 to 55.0) for allocating sepsis patients to the correct triage category. However, specificity was high at 99.4% (95% CI 99.3 to 99.5).

Abstract Background and importanceDetection of sepsis in the emergency department (ED) should be done preferably during triage of the patients. The Manchester triage system (MTS) can be used to screen for sepsis. Objective To investigate the accuracy and validity of the MTS for detection of sepsis during triage in the ED and a combination of the MTS with a SIRS based digital sepsis screening system.DesignSingle center retrospective studySettings and participantsPatients presenting to an ED of a tertiary-care centre who received formal triage were included. (n=29766 patients). Outcome measures and analysisCalculated performance measures included sensitivity, specificity, likelihood ratios and AUC for detection of sepsis. Main resultsA total of 189 (0.7%) subjects met the Sepsis-3 criteria, with 45 cases meeting the criteria for septic shock. The MTS had a low sensitivity of 47.6% (95% CI 40.3 to 55.0) for allocating sepsis patients to the correct triage category. However, specificity was high at 99.4% (95% CI 99.3 to 99.5). Combining the MTS and the SIRS-based screening tool showed an improved sensitivity of 64.0% (95% CI 56.7 to 70.9) and a specificity of 96.8% (95% CI 96.4 to 96.8).

AIMS:We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.METHODS AND RESULTS:In 20 healthy male volunteers (mean age 31 ± 10 years), flow-mediated dilation (FMD) was measured before and after 20 min of arm ischaemia, followed by reperfusion. Remote ischaemic conditioning (RIC) was performed by applying 3 cycles of 5 min of ischaemia of the leg at the onset of index arm ischaemia. Each volunteer underwent the IR-induced vascular injury protocol with and without RIC in a crossover study design. In the control group, IR significantly reduced FMD (5.9 ± 2.9% before IR vs. 2.2 ± 3.7% after IR; p < 0.001). This effect was significantly attenuated by performing RIC (FMD of 5.5 ± 3.1% before IR vs. 4.0 ± 3.4% % after IR; p for interaction = 0.01). Serum levels of SOD and ADMA increased significantly whereas MCP-1 and VEGF levels decreased significantly. Only changes in SOD levels were significantly related to the degree of RIC induced protection (r² = 0.34; p = 0.018).CONCLUSION:RIC has protective effects against endothelial IR injury. Our biomarker study suggests that anti-oxidative stress mediators, such as SOD, seem to be more involved in the pathogenesis of RIC-induced protection in humans than angiogenesis factors or chemo-attractant cytokines.