Sepsis Research Research Articles

The evolution of sepsis publications and global productivity: A bibliometric analysis between 1980 and 2020.

The literature study was conducted by using the Web of Science (WoS) database, employing bibliometric analysis to examine all papers released from 1980 to 2020. The search was performed using the terms "sepsis, septicemia, septic shock" specifically within the titles of the publications. The findings of the literature research revealed a total of 51,725 articles. Out of the total number of publications, 26,896 articles were identified, accounting for 51.9% of the total. The bibliometric study revealed that the United States had the largest number of papers (8693), followed by China (2807), Germany (2299), France (1606), and the United Kingdom (1932). The writers that exhibited the most prolific output in terms of article production on the topic of sepsis were Vincent, with a total of 217 articles, followed by Wang P with 154 articles, and Chaudry IH with 126 articles. The University of Pittsburgh, Brown University, and the University of Michigan were identified as the most productive universities, in that order. The findings from the prediction model revealed that the projected number of articles to be published in 2021 is estimated to be 2086, while the projected number for 2030 is estimated to be 2637. The literature has predominantly focused on disease markers and diagnostic methods, severity and effects of the disease, immunity and inflammation, effects of the disease in neonates and the neonatal period, and treatment and care. According to trend analysis results, recent focus in sepsis research includes a broad spectrum of investigations such as mortality rates, prognostic determinants, diagnostic methods, biomarkers, epidemiological insights, critical care strategies, infections, treatment outcomes, emergency department scenarios, pediatric assessments, and antibiotic interventions.

Bibliometric analysis of neonatal sepsis from 2002 to 2022

AbstractThis study aimed to visualize the knowledge structure and research trends in neonatal sepsis research through bibliometric methods. Articles and reviews regarding neonatal sepsis from 2002 to 2022 were retrieved from the Web of Science Core Collection database. CiteSpace software was used to visualize the knowledge network of countries/regions, institutions, authors, journals, keywords, and references in this field. Altogether, 2314 publications were identified. During the study period, the number of publications increased yearly. The USA is the leading country in neonatal sepsis research. Duke University was the most prolific institution, with Pediatric Infectious Disease Journal and BASU S being the most prolific journal and author in the field, respectively. Pathogen, diagnosis, and management were the main topics of research, and future studies may concentrate on novel diagnostic biomarkers and judicious use of antibiotics. In summary, the results of our bibliometric analysis revealed views on the current situation and trends of neonatal sepsis research for the first time. This study may provide guidance for promoting research on neonatal sepsis.

International Consensus Criteria for Pediatric Sepsis and Septic Shock

Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. To update and evaluate criteria for sepsis and septic shock in children. The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Surviving Sepsis Campaign Research Priorities 2023.

To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

Advancing sepsis clinical research: harnessing transcriptomics for an omics-based strategy - a comprehensive scoping review

Sepsis continues to be recognized as a significant global health challenge across all ages and is characterized by a complex pathophysiology. In this scoping review, PRISMA-ScR guidelines were adhered to, and a transcriptomic methodology was adopted, with the protocol registered on the Open Science Framework. We hypothesized that gene expression analysis could provide a foundation for establishing a clinical research framework for sepsis. A comprehensive search of the PubMed database was conducted with a particular focus on original research and systematic reviews of transcriptomic sepsis studies published between 2012 and 2022. Both coding and non-coding gene expression studies have been included in this review. An effort was made to enhance the understanding of sepsis at the mRNA gene expression level by applying a systems biology approach through transcriptomic analysis. Seven crucial components related to sepsis research were addressed in this study: endotyping (n = 64), biomarker (n = 409), definition (n = 0), diagnosis (n = 1098), progression (n = 124), severity (n = 451), and benchmark (n = 62). These components were classified into two groups, with one focusing on Biomarkers and Endotypes and the other oriented towards clinical aspects. Our review of the selected studies revealed a compelling association between gene transcripts and clinical sepsis, reinforcing the proposed research framework. Nevertheless, challenges have arisen from the lack of consensus in the sepsis terminology employed in research studies and the absence of a comprehensive definition of sepsis. There is a gap in the alignment between the notion of sepsis as a clinical phenomenon and that of laboratory indicators. It is potentially responsible for the variable number of patients within each category. Ideally, future studies should incorporate a transcriptomic perspective. The integration of transcriptomic data with clinical endpoints holds significant potential for advancing sepsis research, facilitating a consensus-driven approach, and enabling the precision management of sepsis.

Sirt3 Deletion Increases Inflammation and Mortality in Polymicrobial Sepsis.

Background: Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that confers resilience to cellular stress by promoting mitochondrial activity. Mitochondrial dysfunction is a major driver of inflammation during sepsis. We hypothesize that Sirt3 expression improves survival in polymicrobial sepsis by mitigating the inflammatory response. Materials and Methods: Sirt3 knockout (S3KO) and wild-type (WT) mice underwent cecal ligation and puncture (CLP) or sham surgery. mRNA expression was quantified using quantitative polymerase chain reaction (qPCR) and protein expression was quantified using enzyme-linked immunosorbent assay (ELISA). Spectrophotometric assays were used to quantify serum markers of organ dysfunction. For in vitro studies, bone marrow-derived macrophages (BMDMs) were harvested from S3KO and WT mice and treated with lipopolysaccharide (LPS). Results: After CLP, hepatic Sirt3 levels decreased from baseline by nine hours and remained depressed at 24 hours. Peak serum interleukin-6 (IL-6) protein levels were higher in S3KO mice. In LPS-treated BMDMs, IL-6 mRNA levels peaked earlier in S3KO cells, although peak levels were comparable to WT. Although S3KO mice had decreased median survival after CLP compared with WT, there was no difference in five-day survival or organ dysfunction. Conclusions: Although S3KO mice initially had increased inflammation and mortality, this difference abated with time, and overall survival was comparable between the groups. This pattern is consistent with the timeline of sepsis-induced Sirt3 downregulation in WT mice, and suggests that Sirt3 downregulation occurring in sepsis is at least partially responsible for the initial hyperinflammatory response and subsequent mortality. Our data support upregulation of Sirt3 as a promising therapeutic strategy for further research in sepsis.

A Prospective Cohort Protocol for the Remnant Investigation in Sepsis Study.

Sepsis is a common and deadly syndrome, accounting for more than 11 million deaths annually. To mature a deeper understanding of the host and pathogen mechanisms contributing to poor outcomes in sepsis, and thereby possibly inform new therapeutic targets, sophisticated, and expensive biorepositories are typically required. We propose that remnant biospecimens are an alternative for mechanistic sepsis research, although the viability and scientific value of such remnants are unknown. The Remnant Biospecimen Investigation in Sepsis study is a prospective cohort study of 225 adults (age ≥ 18 yr) presenting to the emergency department with community sepsis, defined as sepsis-3 criteria within 6 hours of arrival. The primary objective was to determine the scientific value of a remnant biospecimen repository in sepsis linked to clinical phenotyping in the electronic health record. We will study candidate multiomic readouts of sepsis biology, governed by a conceptual model, and determine the precision, accuracy, integrity, and comparability of proteins, small molecules, lipids, and pathogen sequencing in remnant biospecimens compared with paired biospecimens obtained according to research protocols. Paired biospecimens will include plasma from sodium-heparin, EDTA, sodium fluoride, and citrate tubes. The study has received approval from the University of Pittsburgh Human Research Protection Office (Study 21120013). Recruitment began on October 25, 2022, with planned release of primary results anticipated in 2024. Results will be made available to the public, the funders, critical care societies, laboratory medicine scientists, and other researchers.

ADVANCING THE UNDERSTANDING OF CLINICAL SEPSIS USING GENE EXPRESSION-DRIVEN MACHINE LEARNING TO IMPROVE PATIENT OUTCOMES.

Sepsis remains a major challenge that necessitates improved approaches to enhance patient outcomes. This study explored the potential of machine learning (ML) techniques to bridge the gap between clinical data and gene expression information to better predict and understand sepsis. We discuss the application of ML algorithms, including neural networks, deep learning, and ensemble methods, to address key evidence gaps and overcome the challenges in sepsis research. The lack of a clear definition of sepsis is highlighted as a major hurdle, but ML models offer a workaround by focusing on endpoint prediction. We emphasize the significance of gene transcript information and its use in ML models to provide insights into sepsis pathophysiology and biomarker identification. Temporal analysis and integration of gene expression data further enhance the accuracy and predictive capabilities of ML models for sepsis. Although challenges such as interpretability and bias exist, ML research offers exciting prospects for addressing critical clinical problems, improving sepsis management, and advancing precision medicine approaches. Collaborative efforts between clinicians and data scientists are essential for the successful implementation and translation of ML models into clinical practice. Machine learning has the potential to revolutionize our understanding of sepsis and significantly improve patient outcomes. Further research and collaboration between clinicians and data scientists are needed to fully understand the potential of ML in sepsis management.

Research progress of exosomes in the diagnosis and treatment of sepsis

Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.

A bibliometric analysis of exosomes in sepsis from 2004 to 2022.

The study aims to summarize topical and frontier issues in sepsis and exosomes and provide advice and resources for researchers working in related disciplines. Publications on exosomes in sepsis from 2004 to 2022 were extracted from the Web of Science Core Collection database. VOSviewer 1.6.18 and CiteSpace 6.1.3 were used to conduct the bibliometric analysis. The number of publications on exosomes in sepsis showed a rapidly rising trend globally. China and the United States were the most published countries. Shanghai Jiao Tong University is the most prolific institution. Frontiers in Immunology was one of the journals with the highest number of papers. Journal of Immunology was the most co-cited journal. Ping Wang was the most productive author. Clotilde Thery was the author who has been cited the most times among co-cited authors. Singer m, 2016, Jama-j am med assoc was the most co-cited reference. "Mesenchymal stem cells derived exosomes," "microRNAs," "apoptosis," and "immunomodulatory therapy" are the current research hot spots and frontiers. This study provides a comprehensive overview of the current status and trends in sepsis and exosomal research. Researchers working in this area will benefit from the hot spots and trends of exosomes in sepsis discovered through this study.

Aloe-Emodin Ameliorates Cecal Ligation and Puncture-Induced Sepsis.

Sepsis remains a major challenge owing to its severe adverse effects and high mortality, against which specific pharmacological interventions with high efficacy are limited. Mitigation of hyperactive inflammatory responses is a key factor in enhancing the likelihood of survival in patients with sepsis. The Aloe genus has several health benefits, including anti-inflammatory properties. The toxicological implications of aloe-emodin (AE), extracted from various Aloe species, remain uncertain in clinical contexts. However, AE has been shown to inhibit inflammatory responses in lipopolysaccharide-induced mice, indicating its potential as a therapeutic approach for sepsis treatment. Nonetheless, there is a paucity of data regarding the therapeutic benefits of AE in the widely recognized cecal ligation and puncture (CLP)-induced sepsis model, which is commonly used as the gold standard model for sepsis research. This study demonstrates the potential benefits of AE in the treatment of CLP-induced sepsis and investigates its underlying mechanism, along with the efficacy of postoperative AE treatment in mice with CLP-induced sepsis. The results of this study suggest that AE can mitigate sepsis in mice by diminishing systemic inflammation and regulating the gut microbiota. The study provides novel insights into the molecular mechanisms underlying the anti-inflammatory effects of AE.

Bone Marrow Changes in Septic Shock: A Comprehensive Review.

Septic shock is a life-threatening condition characterized by systemic inflammation resulting from a severe infection. Although the primary focus of sepsis research has traditionally been on the dysfunctional immune response, recent studies have highlighted the important role of bone marrow in the pathophysiology of septic shock. The bone marrow, traditionally regarded as the hematopoietic organ responsible for blood cell production, undergoes significant changes during sepsis, contributing to the overall immune dysregulation observed in this condition. This comprehensive review aims to provide a detailed overview of the bone marrow changes associated with septic shock. It explores the alterations in the bone marrow microenvironment, hematopoietic progenitor cells, and the subsequent effects on leukocyte production and function. Key cellular and molecular mechanisms involved in bone marrow dysfunction during septic shock are discussed, including the dysregulation of cytokines, chemokines, growth factors, and signaling pathways. Furthermore, this review highlights the clinical implications of bone marrow changes in septic shock. It emphasizes the impact of altered hematopoiesis on immune cell populations, such as neutrophils, monocytes, and lymphocytes, and their role in the progression and outcome of sepsis. The potential prognostic value of bone marrow parameters and the therapeutic implications of targeting bone marrow dysfunction are also addressed. The review summarizes relevant preclinical and clinical studies to comprehensively understand the current knowledge of bone marrow changes in septic shock. The limitations and challenges of studying bone marrow in the context of sepsis are acknowledged, and future directions for research are proposed.

Enhancing Spns2/S1P in macrophages alleviateshyperinflammation and prevents immunosuppression in sepsis.

Sepsis is a leading cause of in-hospital mortality resulting from a dysregulated response to infection. Novel immunomodulatory therapies targeting macrophage metabolism have emerged as an important focus for current sepsis research. However, understanding the mechanisms underlying macrophage metabolic reprogramming and how they impact immune response requires further investigation. Here, we identify macrophage-expressed Spinster homolog 2 (Spns2), a major transporter of sphingosine-1-phosphate (S1P), as a crucial metabolic mediator that regulates inflammation through the lactate-reactive oxygen species (ROS) axis. Spns2 deficiency in macrophages significantly enhances glycolysis, thereby increasing intracellular lactate production. As a key effector, intracellular lactate promotes pro-inflammatory response by increasing ROS generation. The overactivity of the lactate-ROS axis drives lethal hyperinflammation during the early phase of sepsis. Furthermore, diminished Spns2/S1P signaling impairs the ability of macrophages to sustain an antibacterial response, leading to significant innate immunosuppression in the late stage of infection. Notably, reinforcing Spns2/S1P signaling contributes to balancing the immune response during sepsis, preventing both early hyperinflammation and later immunosuppression, making it a promising therapeutic target for sepsis.

Different Preclinical Animal Models for Sepsis

Sepsis is a significant cause of illness and death, primarily due to the multiple organ dysfunction it can induce. Despite promising results in preclinical studies, most clinical trials testing new treatment strategies for sepsis have failed to show effectiveness. One possible reason for this discrepancy is the misinterpretation of preclinical data, particularly when using animal models that do not adequately mimic human sepsis. This review discusses the potential and limitations of various animal models used in sepsis research, aiming to determine the extent to which these findings are applicable to human sepsis. These animal models encompass different methods such as intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia, and meningitis models. Animal models are crucial in developing new sepsis therapies because they provide essential information about pharmacokinetics, toxicity, and the mechanisms of drug action that cannot be obtained through other means. They offer insights into drugs and initial treatments interact with the body, assess the safety and efficacy of drugs, and investigate the underlying mechanisms of sepsis. However, it is important to acknowledge the limitations of animal models. Animals used in research may not fully replicate the complexity and heterogeneity of human sepsis, leading to differences in treatment response. Ethical considerations also restrict certain invasive procedures in human subjects that can be performed in animal models. These factors contribute to challenges in translating preclinical findings into successful clinical trials.

A model of porcine polymicrobial septic shock

BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.Materials and methodsThe literature search was performed using the keywords “pig”, “sepsis” and “septic shock”. For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.ResultsPublished porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.ConclusionsWe here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.

Research Progress of the Association of the Neutrophil Elastase with Sepsis-related Acute Lung Injury

ABSTRACT Sepsis is considered a life-threatening organ dysfunction resulting from a dysregulation of the body's response to the infection, a syndrome of physiological, pathological, and biochemical abnormalities caused by infection. The prevention and treatment of sepsis-related acute lung injury has become a hot spot in sepsis research in recent years. Neutrophil elastase (NE) is a multifunctional serine protease released by neutrophils cells, which can participate in the regulation of the inflammatory response in the body and directly affect the occurrence and development of inflammation. This article reviews the pathogenesis of sepsis-related lung injury and the mechanism of action, clinical application and prospect of neutrophil elastase inhibitor (NEI).

Facilitating systems-level analyses of all-cause and Covid-mediated sepsis through SeptiSearch, a manually-curated compendium of dysregulated gene sets.

Sepsis is a dysfunctional host response to infection. The syndrome leads to millions of deaths annually (19.7% of all deaths in 2017) and is the cause of most deaths from severe Covid infections. High throughput sequencing or 'omics' experiments in molecular and clinical sepsis research have been widely utilized to identify new diagnostics and therapies. Transcriptomics, quantifying gene expression, has dominated these studies, due to the efficiency of measuring gene expression in tissues and the technical accuracy of technologies like RNA-Seq. Most of these studies seek to uncover novel mechanistic insights into sepsis pathogenesis and diagnostic gene signatures by identifying genes differentially expressed between two or more relevant conditions. However, little effort has been made, to date, to aggregate this knowledge from such studies. In this study we sought to build a compendium of previously described gene sets that combines knowledge gained from sepsis-associated studies. This would enable the identification of genes most associated with sepsis pathogenesis, and the description of the molecular pathways commonly associated with sepsis. PubMed was searched for studies using transcriptomics to characterize acute infection/sepsis and severe sepsis (i.e., sepsis combined with organ failure). Several studies were identified that used transcriptomics to identify differentially expressed (DE) genes, predictive/prognostic signatures, and underlying molecular responses and pathways. The molecules included in each gene set were collected, in addition to the relevant study metadata (e.g., patient groups used for comparison, sample collection time point, tissue type, etc.). After performing extensive literature curation of 74 sepsis-related publications involving transcriptomics, 103 unique gene sets (comprising 20,899 unique genes) from thousands of patients were collated together with associated metadata. Frequently described genes included in gene sets as well as the molecular mechanisms they were involved in were identified. These mechanisms included neutrophil degranulation, generation of second messenger molecules, IL-4 and -13 signaling, and IL-10 signaling among many others. The database, which we named SeptiSearch, is made available in a web application created using the Shiny framework in R, (available at https://septisearch.ca). SeptiSearch provides members of the sepsis community the bioinformatic tools needed to leverage and explore the gene sets contained in the database. This will allow the gene sets to be further scrutinized and analyzed for their enrichment in user-submitted gene expression data and used for validation of in-house gene sets/signatures.

Identification of a novel gene signature for the prognosis of sepsis

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection, and its pathogenesis is still unclear. In view of the complex pathological process of sepsis, finding suitable biomarkers is helpful for the research and treatment of sepsis. This study determined the potential prognostic markers of sepsis by analyzing the molecular characteristics of patients with sepsis. During this study, bioinformatics analysis was conducted on the RNA sequencing data and DNA methylation sites from the public database to determine the prognostic genes related to sepsis, and a 9-gene prognostic signature for sepsis was constructed. According to the risk score, all sepsis samples were divided into two groups. Then, the prediction effect of the 9-gene signature was verified in two cohorts, and the association between these genes and sepsis was further revealed through immune infiltration analysis, gene set enrichment analysis and the relationship between clinical phenotype and survival rate. Our study provided a reliable prognostic signature for sepsis. The signature could predict the survival of patients with sepsis and serve as a predictor.

Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms.

Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it affects over 25 million people every year. Even more severe, septic shock is a subset of sepsis defined by persistent hypotension, and hospital mortality rates are higher than 40%. Although early sepsis mortality has greatly improved in the past few years, sepsis patients who survive the hyperinflammation and subsequent organ damage often die from long-term complications, such as secondary infection, and despite decades of clinical trials targeting this stage of the disease, currently, no sepsis-specific therapies exist. As new pathophysiological mechanisms have been uncovered, immunostimulatory therapy has emerged as a promising path forward. Highly investigated treatment strategies include cytokines and growth factors, immune checkpoint inhibitors, and even cellular therapies. There is much to be learned from related illnesses, and immunotherapy trials in oncology, as well as the recent COVID-19 pandemic, have greatly informed sepsis research. Although the journey ahead is a long one, the stratification of patients according to their immune status and the employment of combination therapies represent a hopeful way forward.

Swiss Sepsis National Action Plan: A coordinated national action plan to stop sepsis-related preventable deaths and to improve the support of people affected by sepsis in Switzerland.

Sepsis is a devastating disease which causes yearly over 10 million deaths worldwide. In 2017, the World Health Organization (WHO) issued a resolution prompting member states to improve the prevention, recognition, and management of sepsis. The 2021 European Sepsis Report revealed that-contrary to other European countries-Switzerland had not yet actioned the sepsis resolution. A panel of experts convened at a policy workshop to address how to improve awareness, prevention, and treatment of sepsis in Switzerland. Goal of the workshop was to formulate a set of consensus recommendations toward creating a Swiss Sepsis National Action Plan (SSNAP). In a first part, stakeholders presented existing international sepsis quality improvement programs and national health programs relevant for sepsis. Thereafter, the participants were allocated into three working groups to identify opportunities, barriers, and solutions on (i) prevention and awareness, (ii) early detection and treatment, and (iii) support for sepsis survivors. Finally, the entire panel summarized the findings from the working groups and identified priorities and strategies for the SSNAP. All discussions during the workshop were transcribed into the present document. All workshop participants and key experts reviewed the document. The panel formulated 14 recommendations to address sepsis in Switzerland. These focused on four domains, including (i) raising awareness in the community, (ii) improving healthcare workforce training on sepsis recognition and sepsis management; (iii) establishing standards for rapid detection, treatment and follow-up in sepsis patients across all age groups; and (iv) promoting sepsis research with particular focus on diagnostic and interventional trials. There is urgency to tackle sepsis. Switzerland has a unique opportunity to leverage from lessons learnt during the COVID-19 pandemic to address sepsis as the major infection-related threat to society. This report details consensus recommendations, the rationale thereof, and key discussion points made by the stakeholders on the workshop day. The report presents a coordinated national action plan to prevent, measure, and sustainably reduce the personal, financial and societal burden, death and disability arising from sepsis in Switzerland.