Een archeologische evaluatie en waardering van het slagveld van Oudenaarde 1708 (Oudenaarde, provincie Oost-Vlaanderen)

Het Ename Expertisecentrum voor Erfgoedontsluiting (EEC) heeft in 2011 en 2012 in opdracht van het agentschap Onroerend Erfgoed en in functie van de mogelijke opmaak van een beschermingsdossier een archeologische evaluatie en waardering uitgevoerd van het slagveld van Oudenaarde 1708. Een eerdere survey uit 2007 onder leiding van de Britse Battlefields Trust had via metaaldetectie het archeologisch potentieel van dit slagveld aangetoond en een doorgedreven onderzoek van het slagveld mogelijk en wenselijk gemaakt. Het veldwerk werd uitgevoerd van 12 september tot 31 oktober 2011. De studie maakte een aanzienlijke vooruitgang in het begrijpen van de veldslag en in het plaatsen van de actie op het terrein, en liet toe om de aard, de toestand en de verspreiding van de archeologische zone te bepalen en de problemen die dit oplevert. Terzelfdertijd heeft dit werk inzicht gegeven in de praktische problemen op het veld, en een strategie opgeleverd voor verder onderzoek. De belangrijkste primaire bronnen van de veldslag werden samengebracht en vertaald en de grafische en geschreven bronnen werden in een redelijk accurate weergave van het landschap geplaatst zoals het er ten tijde van de veldslag moet hebben uitgezien. Oudenaarde bleek een ongewoon complexe veldslag met een opmerkelijke wisselwerking tussen het terrein en de acties. Door de goede staat van bewaring van het merendeel van het slagveld kan Oudenaarde van aanzienlijk belang zijn bij de verdere ontwikkeling van slagveldarcheologie. De kogels zijn weliswaar relatief slecht bewaard, maar toch nog voldoende goed om een adequate analyse van de inslagschade te bekomen. Het gebruik als akkerland sinds de late 18e eeuw had een ernstige destructief effect op slagveldartefacten. Het losmaken van de grond en diep ploegen is wellicht ook zeer destructief voor eventuele massagraven. Het permanent grasland op een beperkt deel van het terrein tempert wel de snelheid van verval van de artefacten, aangezien zowel verluchting van de grond als mechanische schade hierdoor vermeden wordt. De studie eindigt met aanbevelingen over de mogelijke begrenzing van de archeologische zone en stelt ook maatregelen voor naar beheer en behoud van de site

Interrater agreement in classifying infections during extracorporeal membrane oxygenation

Infectious complications are common during extracorporeal membrane oxygenation (ECMO) and may negatively impact outcomes. However, there is considerable variation in the reported rates of incidence, which hampers the use of infections as a quality benchmark for ECMO centers. To assess the contributing role of poor interrater agreement, three independent raters reviewed medical records from all intensive care unit (ICU) patients who received ECMO for &gt;24 h in our tertiary center between October 2019 and October 2021 for suspected episodes of infection, which were rated based on their date of onset and presumed site/diagnosis. To establish a gold standard, any discrepancies were resolved using an expert panel consisting of two intensivists/infectious disease specialists. During 83 ECMO-runs in 77 patients, we observed a total of 62 adjudicated infectious episodes (incidence rate 62, 95% CI: 48–80, per 1000 days at risk). Among 81 episodes suspected by at least one observer, 66 (81%) were identified by two, and only 44 (54%) by all three raters, resulting in Fleiss’ kappa of 0.10 (95% CI: 0.00–0.19; slight agreement). However, if raters concurred regarding infection onset, subsequent agreement on infection site was good (concordance 89%; kappa 0.85, 95% CI: 0.72–0.98; near perfect agreement). In conclusion, adjudication of infectious episodes during ECMO is associated with poor interrater agreement regarding occurrence—but not site—of infection. This finding might partially explain the significant disparities observed in reported infection rates during ECMO, emphasizing the need for caution when interpreting infection data in this particular population due to the potential for inherent measurement error.</p

The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella

Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Interrater agreement in classifying infections during extracorporeal membrane oxygenation

Infectious complications are common during extracorporeal membrane oxygenation (ECMO) and may negatively impact outcomes. However, there is considerable variation in the reported rates of incidence, which hampers the use of infections as a quality benchmark for ECMO centers. To assess the contributing role of poor interrater agreement, three independent raters reviewed medical records from all intensive care unit (ICU) patients who received ECMO for >24 h in our tertiary center between October 2019 and October 2021 for suspected episodes of infection, which were rated based on their date of onset and presumed site/diagnosis. To establish a gold standard, any discrepancies were resolved using an expert panel consisting of two intensivists/infectious disease specialists. During 83 ECMO-runs in 77 patients, we observed a total of 62 adjudicated infectious episodes (incidence rate 62, 95% CI: 48–80, per 1000 days at risk). Among 81 episodes suspected by at least one observer, 66 (81%) were identified by two, and only 44 (54%) by all three raters, resulting in Fleiss’ kappa of 0.10 (95% CI: 0.00–0.19; slight agreement). However, if raters concurred regarding infection onset, subsequent agreement on infection site was good (concordance 89%; kappa 0.85, 95% CI: 0.72–0.98; near perfect agreement). In conclusion, adjudication of infectious episodes during ECMO is associated with poor interrater agreement regarding occurrence—but not site—of infection. This finding might partially explain the significant disparities observed in reported infection rates during ECMO, emphasizing the need for caution when interpreting infection data in this particular population due to the potential for inherent measurement error

A guide to immunotherapy for COVID-19

Immune dysregulation is an important component of the pathophysiology of COVID-19. A large body of literature has reported the effect of immune-based therapies in patients with COVID-19, with some remarkable successes such as the use of steroids or anti-cytokine therapies. However, challenges in clinical decision-making arise from the complexity of the disease phenotypes and patient heterogeneity, as well as the variable quality of evidence from immunotherapy studies. This Review aims to support clinical decision-making by providing an overview of the evidence generated by major clinical trials of host-directed therapy. We discuss patient stratification and propose an algorithm to guide the use of immunotherapy strategies in the clinic. This will not only help guide treatment decisions, but may also help to design future trials that investigate immunotherapy in other severe infections

Reframing Sepsis Immunobiology for Translation

Sepsis is a common and deadly condition. The current framing of dysregulated host immune responses within the sepsis immunobiology model into pro-inflammatory and immunosuppressive responses for testing novel treatments, have not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalized immunomodulation. In this perspective we highlight that many fundamental immunological concepts such as resistance, disease tolerance, resilience, resolution, and repair are not incorporated into the current sepsis immunobiology model. The focus for addressing heterogeneity in sepsis should broaden beyond subtyping, onto identifying deterministic molecularnetworks or dominant mechanisms. We explicitly reframe the dysregulated host immune responses in sepsis as pathologic disruption and/or alteration in homeostasis of the immune-driven resistance, tolerance and resolution mechanisms occurring concurrently. Our reframing highlights novel treatment opportunities and could enable successful immunomodulation in the future.Keywords: Sepsis, immunobiology, precision medicine, molecular mechanisms, subtyping, immunomodulation<br/

[18F]FDG PET/CT identifies infectious and inflammatory foci in persistent critical illness.

PURPOSE: Some ICU patients remain critically ill despite reversal of the original admission diagnosis, driven by a cascade of events resulting in new and persistent organ failure. Secondary infections and systemic inflammation are important components of this cascade and may be visualised using [ 18F]FDG PET/CT. The aim of this dual centre retrospective study was to assess the ability of [ 18F]FDG PET/CT to identify infectious and inflammatory foci in patients with persistent critical illness and to evaluate its impact on subsequent therapy management. METHODS: We included patients admitted to the ICU between 2017 and 2024, in whom a [ 18F]FDG PET/CT scan was performed ten days or more after ICU admission. [ 18F]FDG PET/CT reports were reviewed for diagnoses, and clinical records were reviewed to determine if this diagnosis was new, which diagnostics were performed before the PET/CT, and which therapeutic changes were made directly after the PET/CT. The relation between inflammatory parameters and [ 18F]FDG PET/CT findings were studied using t-test or ANOVA. RESULTS: Forty-seven patients with persistent critical illness were included from two university medical centres. The median interval between admission and PET/CT was 21 days (IQR 14-28). In 43 patients (91%) a potential infectious or inflammatory focus was detected, of which 34 (72%) were previously unknown. The [ 18F]FDG PET/CT was utilized late in the diagnostic work-up since a median of 7 (IQR 6.0-8.0) diagnostic procedures were performed prior to the PET/CT. In 26 (55%) patients therapy change was reported within 48 h after the PET/CT. CONCLUSION: [ 18F]FDG PET/CT detected a considerable number of (new) infectious and inflammatory foci in patients with persistent critical illness, often followed by a change in therapy. Further research is needed to establish the role of [ 18F]FDG PET/CT in these patients

Dysregulated innate and adaptive immune responses discriminate disease severity in COVID-19

The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive pro-inflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis reveals no specific inflammatory endotypes in COVID-19 patients. Functional assays reveal abrogated adaptive cytokine production (interferon-gamma, interleukin-17 and interleukin-22) and prominent T cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlight potential biomarkers of disease severity