Plasma proteomics identifies molecular subtypes in sepsis.

Background: The heterogeneity of sepsis represents a significant challenge to the development of personalized sepsis therapies. Sepsis subtyping has therefore emerged as an important approach to this problem, but its impact on clinical practice was limited due to insufficient molecular insights. Modern proteomics techniques allow the identification of subtypes and provide molecular and mechanistical insights.

Machine learning identifies clinical sepsis phenotypes that translate to the plasma proteome.

Background: Sepsis therapy is still limited to treatment of the underlying infection and supportive measures. To date, various sepsis subtypes were proposed, but therapeutic options addressing the molecular changes of sepsis were not identified. With the aim of a future individualized therapy, we used machine learning (ML) to identify clinical phenotypes and their temporal development in a prospective, multicenter sepsis cohort and characterized them using plasma proteomics.

Impact of glucocorticoid receptor polymorphism rs6198 on sepsis survival in a prospective multicenter cohort.

The glucocorticoid receptor (GR), particularly its isoforms GRα and GRβ, plays a crucial role in modulating inflammatory responses. The rs6198 single nucleotide polymorphism (SNP) in the NR3C1 gene, which encodes GR, has been associated with adverse outcomes in various diseases due to its potential effect on GR isoform expression. This study aims to explore the impact of the rs6198 SNP in sepsis.

Improving AI-Based Clinical Decision Support Systems and Their Integration Into Care From the Perspective of Experts: Interview Study Among Different Stakeholders.

Background: Artificial intelligence (AI)-based systems are receiving increasing attention in the health care sector. While the use of AI is well advanced in some medical applications, such as image recognition, it is still in its infancy in others, such as clinical decision support systems (CDSS). Examples of AI-based CDSS can be found in the context of sepsis prediction or antibiotic prescription.

The Actual Clinical Situation Ruthlessly Exposes the Challenge of Rational Care for Nosocomial and Community-Acquired Infections and Requires Even More Efforts for Satisfactory Antibiotic Stewardship.

Antimicrobial resistance is one of the 10 most pressing health problems worldwide. First steps toward harnessing the complex dynamics of antibiotic resistance are presented. To accomplish this, we first shift down a gear and try to understand the actual driving dynamics behind the development of resistance in a specific clinical department.

The protein interaction of mitochondrial transcription factors A and B2 is associated with 30-day survival in critical COVID-19.

Introduction: Repair of mitochondrial damage seems pivotal for clinical recovery and determining outcome in patients with critical COVID-19. However, reliable biomarkers for non-invasively assessing mitochondrial repair in peripheral blood of critically ill COVID-19 patients are currently lacking. Accordingly, we sought to assess different surrogates of mitochondrial repair in peripheral blood and correlate these measurements with clinical outcome in patients with critical COVID-19.

Host Biomarkers and Antibiotic Tissue Penetration in Sepsis: Insights from Moxifloxacin.

Background And Objective: Sepsis-induced pathophysiological changes may lead to pharmacokinetic variability which alters antibiotic concentrations at the host infection site. This poses a challenge in clinical practice, as sufficient antibiotic concentrations in tissue are necessary to effectively eradicate bacterial pathogens. In this exploratory study, we aimed to evaluate the potential of routinely used laboratory biomarkers to predict subcutaneous and muscle tissue penetration of moxifloxacin in septic patients.

Subphenotypes and the De Ritis ratio for mortality risk stratification in sepsis-associated acute liver injury: a retrospective cohort study.

Background: Sepsis-associated liver injury (SALI) is associated with poor outcomes and increased mortality. However, effectively stratifying SALI patients according to prognosis remains challenging. This study evaluates laboratory-based clustering filters for stratifying SALI patients by 30-day mortality risk, utilizing data mining techniques for novel pattern discovery.

Problems and Barriers Related to the Use of AI-Based Clinical Decision Support Systems: Interview Study.

Background: Digitalization is currently revolutionizing health care worldwide. A promising technology in this context is artificial intelligence (AI). The application of AI can support health care providers in their daily work in various ways.

User-Oriented Requirements for Artificial Intelligence-Based Clinical Decision Support Systems in Sepsis: Protocol for a Multimethod Research Project.

Background: Artificial intelligence (AI)-based clinical decision support systems (CDSS) have been developed for several diseases. However, despite the potential to improve the quality of care and thereby positively impact patient-relevant outcomes, the majority of AI-based CDSS have not been adopted in standard care. Possible reasons for this include barriers in the implementation and a nonuser-oriented development approach, resulting in reduced user acceptance.

Employing artificial intelligence for optimising antibiotic dosages in sepsis on intensive care unit: a study protocol for a prospective observational study (KI.SEP).

Introduction: In sepsis treatment, achieving and maintaining effective antibiotic therapy is crucial. However, optimal antibiotic dosing faces challenges due to significant variability among patients with sepsis. Therapeutic drug monitoring (TDM), the current gold standard, lacks initial dosage adjustments and global availability.

Concentrations of ceftazidime and avibactam in bile fluid-a prospective phase IIb study.

Background: The rise in carbapenem-resistant bacteria and the limited number of effective antibiotics pose a major health-care threat. The combination of ceftazidime (CAZ) and avibactam (AVI) represents an approved treatment option for carbapenem-resistant intra-abdominal infections. However, data on the pharmacokinetic profile of AVI in the hepatobiliary compartment is lacking.

Predictive enrichment for the need of renal replacement in sepsis-associated acute kidney injury: combination of furosemide stress test and urinary biomarkers TIMP-2 and IGFBP-7.

Background: In sepsis, initial resuscitation with fluids is followed by efforts to achieve a negative fluid balance. However, patients with sepsis-associated acute kidney injury (SA-AKI) often need diuretic or renal replacement therapy (RRT). The dilemma is to predict whether early RRT might be advantageous or diuretics will suffice.

Activation of the MAPK network provides a survival advantage during the course of COVID-19-induced sepsis: a real-world evidence analysis of a multicenter COVID-19 Sepsis Cohort.

Purpose: There is evidence that lower activity of the RAF/MEK/ERK network is associated with positive outcomes in mild and moderate courses of COVID-19. The effect of this cascade in COVID-19 sepsis is still undetermined. Therefore, we tested the hypothesis that activity of the RAF/MEK/ERK network in COVID-19-induced sepsis is associated with an impact on 30-day survival.

Exploring the relationship between HCMV serostatus and outcomes in COVID-19 sepsis.

Background: Sepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19.

The Association between the rs3747406 Polymorphism in the Glucocorticoid-Induced Leucine Zipper Gene and Sepsis Survivals Depends on the SOFA Score.

The variability in mortality in sepsis could be a consequence of genetic variability. The glucocorticoid system and the intermediate TSC22D3 gene product-glucocorticoid-induced leucine zipper-are clinically relevant in sepsis, which is why this study aimed to clarify whether TSC22D3 gene polymorphisms contribute to the variance in sepsis mortality. Blood samples for DNA extraction were obtained from 455 patients with a sepsis diagnosis according to the Sepsis-III criteria and from 73 control subjects.

The Aquaporin 3 Polymorphism (rs17553719) Is Associated with Sepsis Survival and Correlated with IL-33 Secretion.

Sepsis is a common life-threatening disease caused by dysregulated immune response and metabolic acidosis which lead to organ failure. An abnormal expression of aquaporins plays an important role in organ failure. Additionally, genetic variants in aquaporins impact on the outcome in sepsis.

AQP3 and AQP9-Contrary Players in Sepsis?

Sepsis involves an immunological systemic response to a microbial pathogenic insult, leading to a cascade of interconnected biochemical, cellular, and organ-organ interaction networks. Potential drug targets can depict aquaporins, as they are involved in immunological processes. In immune cells, AQP3 and AQP9 are of special interest.

Increased prevalence of clonal hematopoiesis of indeterminate potential in hospitalized patients with COVID-19.

Clonal hematopoiesis of indeterminate potential (CHIP) leads to higher mortality, carries a cardiovascular risk and alters inflammation. All three aspects harbor overlaps with the clinical manifestation of COVID-19. This study aimed to identify the impact of CHIP on COVID-19 pathophysiology.

The Distinctive Activation of Toll-Like Receptor 4 in Human Samples with Sepsis.

Clinical success of Toll-Like receptor-4 (TLR-4) antagonists in sepsis therapy has thus far been lacking. As inhibition of a receptor can only be useful if the receptor is active, stratification of patients with active TLR-4 would be desirable. Our aim was to establish an assay to quantify phosphorylated TLR-4 using the proximity ligation assay (PLA).

Therapeutic Suggestions During General Anesthesia Reduce Postoperative Nausea and Vomiting in High-Risk Patients - A Analysis of a Randomized Controlled Trial.

Postoperative nausea and vomiting (PONV) are one of the most adverse events after general anesthesia, a distressing experience, and pose a risk to the patient. Despite advances in drug prophylaxis and PONV treatment, the incidence remains high and additional non-pharmacological treatments are needed. In this analysis of a recently published double-blind multicenter randomized controlled trial on the efficacy of intraoperative therapeutic suggestions on postoperative opioid dosage, we analyzed the effects of intraoperative therapeutic suggestions on PONV.

The Pro-Inflammatory Deletion Allele of the NF-κB1 Polymorphism Is Characterized by a Depletion of Subunit p50 in Sepsis.

The functionally important NF-κB1 promoter polymorphism (-94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both healthy volunteers ( = 20) and septic patients ( = 10).