F.E. van Beuningen’s research while affiliated with University of Groningen and other places

Sepsis is a dysregulated host response to an infection, characterized by organ failure. The pathophysiology is complex and incompletely understood, but mitochondria appear to play a key role in the cascade of events that culminate in multiple organ failure and potentially death. In shaping immune responses, mitochondria fulfil dual roles: they not only supply energy and metabolic intermediates crucial for immune cell activation and function but also influence inflammatory and cell death pathways. Importantly, mitochondrial dysfunction has a dual impact, compromising both immune system efficiency and the metabolic stability of end organs. Dysfunctional mitochondria contribute to the development of a hyperinflammatory state and loss of cellular homeostasis, resulting in poor clinical outcomes. Already in early sepsis, signs of mitochondrial dysfunction are apparent and consequently, strategies to optimize mitochondrial function in sepsis should not only prevent the occurrence of mitochondrial dysfunction, but also cover the repair of the sustained mitochondrial damage. Here, we discuss mitochondrial quality control (mtQC) in the pathogenesis of sepsis and exemplify how mtQC could serve as therapeutic target to overcome mitochondrial dysfunction. Hence, replacing or repairing dysfunctional mitochondria may contribute to the recovery of organ function in sepsis. Mitochondrial biogenesis is a process that results in the formation of new mitochondria and is critical for maintaining a pool of healthy mitochondria. However, exacerbated biogenesis during early sepsis can result in accumulation of structurally aberrant mitochondria that fail to restore bioenergetics, produce excess reactive oxygen species (ROS) and exacerbate the disease course. Conversely, enhancing mitophagy can protect against organ damage by limiting the release of mitochondrial-derived damage-associated molecules (DAMPs). Furthermore, promoting mitophagy may facilitate the growth of healthy mitochondria by blocking the replication of damaged mitochondria and allow for post sepsis organ recovery through enabling mitophagy-coupled biogenesis. The remaining healthy mitochondria may provide an undamaged scaffold to reproduce functional mitochondria. However, the kinetics of mtQC in sepsis, specifically mitophagy, and the optimal timing for intervention remain poorly understood. This review emphasizes the importance of integrating mitophagy induction with mtQC mechanisms to prevent undesired effects associated with solely the induction of mitochondrial biogenesis.

Sepsis is a dysregulated host response to infection that can lead to life‐threatening organ failure. Circulating bacterial toxins, termed pathogen‐associated molecular patterns (PAMPs), and excess cytokines produced by the immune system play a key role in the response that can progress into organ failure. Yet, no therapy is available to effectively remove these PAMPs and cytokines from the circulation or effectively block their action. Macrophage membrane coatings possess a natural blood compatibility, ideal for coating of adsorbent surfaces in extracorporeal blood‐cleansing. Here, the ability of Escherichia coli‐activated macrophage membrane coatings on silicon nanowired (SiNW) surfaces in a microfluidic device to remove PAMPs and cytokines from blood is determined. In vitro, such membrane‐coated SiNW adsorbent surfaces remove significantly more PAMPS or cytokines from spiked human blood than achieved by hemofiltration. Cleansing of plasma from patients with bacterial sepsis using membrane‐coated SiNW adsorbent surfaces reduces cytokine concentrations to healthy levels. In vivo, this coincides with two‐fold better restoration of healthy cytokine levels after 4 h of extracorporeal blood‐cleansing in rats with lipopolysaccharides (LPS)‐induced sepsis and four‐fold higher survival rates. Collectively, blood‐cleansing microfluidic devices using bacterially activate macrophage membrane‐coated SiNW surfaces are more effective than hemofiltration for therapeutic intervention in septic patients.

Aim The aim of this study was to examine the quality of manuscripts reporting sepsis health care costs and to provide an overview of hospital-related expenditures for sepsis in adult patients around the world. Methods We systematically searched the PubMed, EMBASE, Cochrane and Google Scholar to identify relevant studies between January 2010 and January 2022. We selected articles that provided costs and cost-effectiveness analyses, defined sepsis and described their cost calculation method. All costs were adjusted to 2020 US dollars. Medians and interquartile ranges (IQRs) for various costs of sepsis were calculated. The quality of economic studies was assessed using the Drummond 10-item checklist. Results Overall, 26 studies met our eligibility criteria. The mean total hospital costs per patient varied largely, between €1101 and €91,951. The median (IQR) of the total sepsis costs per country were €36,191 (€17,158 - €53,349), which equals €50 (€34 - €84) per capita annually. The relative amount of healthcare budget spent on sepsis was 2.65%, which equals 0.33% of the gross national product (GNP). Conclusion While general sepsis costs are high, there is considerable variability between countries regarding the costs of sepsis. Further studies examining the impact on sepsis costs, especially on the general ward, can help justify, design and monitor initiatives on prevention, diagnosis, and treatment of this time-critical and potentially preventable disease.

Purpose Research in acute care faces many challenges, including enrolment challenges, legal limitations in data sharing, limited funding and lack of singular ownership of the domain of acute care. To overcome these challenges, the Center of Acute Care of the University Medical Center Groningen in the Netherlands, has established a de novo data, image and biobank named ‘Acutelines’. Participants Clinical data, imaging data and biomaterials (ie, blood, urine, faeces, hair) are collected from patients presenting to the emergency department (ED) with a broad range of acute disease presentations. A deferred consent procedure (by proxy) is in place to allow collecting data and biomaterials prior to obtaining written consent. The digital infrastructure used ensures automated capturing of all bed-side monitoring data (ie, vital parameters, electrophysiological waveforms) and securely importing data from other sources, such as the electronic health records of the hospital, ambulance and general practitioner, municipal registration and pharmacy. Data are collected from all included participants during the first 72 hours of their hospitalisation, while follow-up data are collected at 3 months, 1 year, 2 years and 5 years after their ED visit. Findings to date Enrolment of the first participant occurred on 1 September 2020. During the first month, 653 participants were screened for eligibility, of which 180 were approached as potential participants. In total, 151 (84%) provided consent for participation of which 89 participants fulfilled criteria for collection of biomaterials. Future plans The main aim of Acutelines is to facilitate research in acute medicine by providing the framework for novel studies and issuing data, images and biomaterials for future research. The protocol will be extended by connecting with central registries to obtain long-term follow-up data, for which we already request permission from the participant. Trial registration number NCT04615065 .

The Advisory Council on International Affairs (AIV) is an advisory body of the Dutch government and parliament. In particular its reports address the policy of the Ministry of Foreign Affairs, the Minister of Defence, the Minister for Development Co-operation and the State Secretary of Foreign Affairs. In mid-2001 the Dutch government asked the AIV to produce an advisory report on the Organisation for Security and Co-operation in Europe (OSCE) in the light of the Dutch Chairmanship of the organisation in the year 2003. The following article is a recapitulation of the findings and recommendations of the AIV as presented to the Dutch government on 3 rd May 2002. English and Russian translations of the report re available and can be obtained from the Secretariat of the Advisory Council on International Affairs (E-mail: [email protected] /* */ or P.O. Box 20061, 2500 EB The Hague, the Netherlands).