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Project description:Infective endocarditis is a severe disease caused by the infection of heart valves and endocardium by pathogenic germ. Antimicrobial therapy and surgery remain the basis of treatment, and up to 50% of the patients require surgical replacement of the affected valves to control the infectious source. The objective of this work is to identify the existence of endotypes in a prospective cohort of patients with infective endocarditis. We performed a bulk RNA-seq form peripheral blood to cluster patients according to their transcriptomic profiles at diagnosis and during their follow-up. Clinical data, outcomes and response to surgery were assessed in a cluster-specific manner, in order to identify differences in the pathogenesis that could help to find personalized treatments and improve the outcome.
2023-08-08 | GSE240319 | GEO
Project description:Infective endocarditis is a severe disease caused by the infection of heart valves and endocardium by pathogenic germ. Antimicrobial therapy and surgery remain the basis of treatment, and up to 50% of the patients require surgical replacement of the affected valves to control the infectious source. The objective of this work is to identify the existence of endotypes in a prospective cohort of patients with infective endocarditis. We performed a bulk RNA-seq form peripheral blood to cluster patients according to their transcriptomic profiles at diagnosis and during their follow-up. Clinical data, outcomes and response to surgery were assessed in a cluster-specific manner, in order to identify differences in the pathogenesis that could help to find personalized treatments and improve the outcome.
2023-08-08 | GSE240320 | GEO
Project description:Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis
| PRJNA1003144 | ENA
Project description:Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis [pre]
| PRJNA1003148 | ENA
Project description:Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis [pre-post_qx]
| PRJNA1003147 | ENA
Project description:BackgroundSepsis is a heterogeneous syndrome due to a variable range of dysregulated processes in the host immune response. Efforts are made to stratify patients for personalized immune-based treatments and better prognostic prediction. Using gene expression data, different inflammatory profiles have been identified. However, it remains unknown whether these endotypes mirror inflammatory proteome profiling, which would be more feasible to assess in clinical practice. We aim to identify different inflammatory endotypes based on circulating proteins in a cohort of moderately ill patients with severe infection (Sepsis-2 criteria).MethodsIn this prospective study, 92 inflammatory plasma markers were profiled using a targeted proteome platform and compared between patients with severe infection (Sepsis-2 criteria) and healthy controls. To identify endotypes with different inflammatory profiles, we performed hierarchical clustering of patients based on the differentially expressed proteins, followed by clinical and demographic characterization of the observed endotypes.ResultsIn a cohort of 167 patients with severe infection and 192 healthy individuals, we found 62 differentially expressed proteins. Inflammatory proteins such as TNFSF14, OSM, CCL23, IL-6, and HGF were upregulated, while TRANCE, DNER and SCF were downregulated in patients. Unsupervised clustering identified two different inflammatory profiles. One endotype showed significantly higher inflammatory protein abundance, and patients with this endotype were older and showed lower lymphocyte counts compared to the low inflammatory endotype.ConclusionsBy identifying endotypes based on inflammatory proteins in moderately ill patients with severe infection, our study suggests that inflammatory proteome profiling can be useful for patient stratification.
| S-EPMC9547371 | biostudies-literature
Project description:BackgroundInfective endocarditis (IE) in South Africa is associated with significant morbidity and mortality, despite occurring in younger patients with fewer co-morbidities. Possible contributors include the high rates of blood culture negative endocarditis, high rates of mechanical valve replacement and the lack of inter-disciplinary coordination during management.MethodsThe Tygerberg Endocarditis Cohort (TEC) study prospectively enrolled patients with IE between November 2019 and April 2021. All patients were managed by an Endocarditis Team with a set protocol for organism detection and a strategy of early surgery limiting the use of prosthetic material.ResultsSeventy-two consecutive patients with IE were included, with a causative organism identified in 86.1% of patients. The majority of patients had a guideline indication for surgery (n=58; 80.6%). The in-hospital mortality rate was 18%, with a 6-month mortality rate of 25.7%. Surgery was performed in 42 patients (58.3%), with prosthetic valve (PVE) replacement in 32 (76.2%), conventional repair surgery in 8 (19.1%) and mitral valve reconstruction in 2 (4.8%) of patients. Patients who underwent surgery had a significantly lower in-hospital (4.8% vs. 56.3%; P<0.01) and 6-month (4.9% vs. 75.0%; P<0.01) mortality rate as compared with patients with an indication for surgery who did not undergo surgery.ConclusionsWe have observed a reduction in the 6-month mortality rate in patients with IE following the establishment of an Endocarditis Team, adhering to a set protocol for organism detection and favouring early repair or reconstruction surgery. Patients who underwent surgery had a significantly lower mortality rate than patients with an indication for surgery who did not undergo surgery. Preventable residual mortality was driven by surgical delay.
| S-EPMC9412218 | biostudies-literature
Project description:BACKGROUND:Polymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies, a chronic inflammatory disorder clinically characterized by muscle weakness and inflammatory cell infiltrates in muscle tissue. In PM, a major component of inflammatory cell infiltrates is CD8+ T cells, whereas in DM, CD4+ T cells, plasmacytoid dendritic cells, and B cells predominate. In this study, with the aim to differentiate involvement of CD4+ and CD8+ T-cell subpopulations in myositis subgroups, we investigated transcriptomic profiles of T cells from peripheral blood of patients with myositis. METHODS:Total RNA was extracted from CD4+ T cells (PM?=?8 and DM?=?7) and CD8+ T cells (PM?=?4 and DM?=?5) that were isolated from peripheral blood mononuclear cells via positive selection using microbeads. Sequencing libraries were generated using the Illumina TruSeq Stranded Total RNA Kit and sequenced on an Illumina HiSeq 2500 platform, yielding about 50 million paired-end reads per sample. Differential gene expression analyses were conducted using DESeq2. RESULTS:In CD4+ T cells, only two genes, ANKRD55 and S100B, were expressed significantly higher in patients with PM than in patients with DM (false discovery rate [FDR]?<?0.05, model adjusted for age, sex, HLA-DRB1*03 status, and RNA integrity number [RIN]). On the contrary, in CD8+ T cells, 176 genes were differentially expressed in patients with PM compared with patients with DM. Of these, 44 genes were expressed significantly higher in CD8+ T cells from patients with PM, and 132 genes were expressed significantly higher in CD8+ T cells from patients with DM (FDR?<?0.05, model adjusted for age, sex, and RIN). Gene Ontology analysis showed that genes differentially expressed in CD8+ T cells are involved in lymphocyte migration and regulation of T-cell differentiation. CONCLUSIONS:Our data strongly suggest that CD8+ T cells represent a major divergence between PM and DM patients compared with CD4+ T cells. These alterations in the gene expression in T cells from PM and DM patients might advocate for distinct immune mechanisms in these subphenotypes of myositis.
| S-EPMC6116372 | biostudies-literature
Project description:To update the epidemiology of S. aureus bloodstream infection (SAB) in a high-income country and its link with infective endocarditis (IE).All consecutive adult patients with incident SAB (n = 2008) were prospectively enrolled between 2009 and 2011 in 8 university hospitals in France.SAB was nosocomial in 54%, non-nosocomial healthcare related in 18% and community-acquired in 26%. Methicillin resistance was present in 19% of isolates. SAB Incidence of nosocomial SAB was 0.159/1000 patients-days of hospitalization (95% confidence interval [CI] 0.111-0.219). A deep focus of infection was detected in 37%, the two most frequent were IE (11%) and pneumonia (8%). The higher rates of IE were observed in injecting drug users (IE: 38%) and patients with prosthetic (IE: 33%) or native valve disease (IE: 20%) but 40% of IE occurred in patients without heart disease nor injecting drug use. IE was more frequent in case of community-acquired (IE: 21%, adjusted odds-ratio (aOR) = 2.9, CI = 2.0-4.3) or non-nosocomial healthcare-related SAB (IE: 12%, aOR = 2.3, CI = 1.4-3.5). S. aureus meningitis (IE: 59%), persistent bacteremia at 48 hours (IE: 25%) and C-reactive protein > 190 mg/L (IE: 15%) were also independently associated with IE. Criteria for severe sepsis or septic shock were met in 30% of SAB without IE (overall in hospital mortality rate 24%) and in 51% of IE (overall in hospital mortality rate 35%).SAB is still a severe disease, mostly related to healthcare in a high-income country. IE is the most frequent complication and occurs frequently in patients without known predisposing conditions.
| S-EPMC4447452 | biostudies-other
Project description:Background: Sepsis is a heterogenous syndrome with limited therapeutic options. Identifying characteristic gene expression patterns, or endotypes, in septic patients may lead to targeted interventions. We investigated whether patients admitted to a surgical ICU with sepsis and with high risk of mortality express similar endotypes to non-septic, but still critically ill patients using two multiplex transcriptomic metrics obtained both on admission to a surgical intensive care unit (ICU) and at set intervals. Methods: We analyzed transcriptomic data from 522 patients in two single-site, prospective, observational cohorts admitted to surgical ICUs over a 5-year period ending in July 2020 . Using an FDA-cleared analytical platform (nCounter FLEX ® , NanoString, Inc.), we assessed a previously validated 29-messenger RNA transcriptomic classifier for likelihood of 30-day mortality (IMX-SEV-3) and a 33-messenger RNA transcriptomic endotype classifier. Clinical outcomes included all-cause (in-hospital, 30-, 90-day) mortality, development of chronic critical illness (CCI), and secondary infections. Univariate and multivariate analyses were performed to assess for true effect and confounding. Results: Sepsis was associated with a significantly higher predicted and actual hospital mortality. At enrollment, the predominant endotype for both septic and non-septic patients was adaptive , though with significantly different distributions. Inflammopathic and coagulopathic septic patients, as well as inflammopathic non-septic patients, showed significantly higher frequencies of secondary infections compared to those with adaptive endotypes (p<0.01). Endotypes changed during ICU hospitalization in 57.5% of patients. Patients who remained adaptive had overall better prognosis, while those who remained inflammopathic or coagulopathic had worse overall outcomes. For severity metrics, patients admitted with sepsis and a high predicted likelihood of mortality showed an inflammopathic (49.6%) endotype and had higher rates of cumulative adverse outcomes (67.4%). Patients at low mortality risk, whether septic or non-septic, almost uniformly presented with an adaptive endotype (100% and 93.4%, respectively). Conclusion : Critically ill surgical patients express different and evolving immunological endotypes depending upon both their sepsis status and severity of their clinical course. Future studies will elucidate whether endotyping critically ill, septic patients can identify individuals for targeted therapeutic interventions to improve patient management and outcomes.
| S-EPMC10197751 | biostudies-literature