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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: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:This SuperSeries is composed of the SubSeries listed below.
2020-06-23 | GSE152980 | GEO
Project description:Infective endocarditis (IE) complicating hypertrophic cardiomyopathy (HCM) is a poorly known entity. Although current guidelines do not recommend IE antibiotic prophylaxis (IEAP) in HCM, controversy remains.This study sought to describe the clinical course of a large series of IE HCM and to compare IE in HCM patients with IE patients with and without an indication for IEAP.Data from the GAMES IE registry involving 27 Spanish hospitals were analyzed. From January 2008 to December 2013, 2000 consecutive IE patients were prospectively included in the registry. Eleven IE HCM additional cases from before 2008 were also studied. Clinical, microbiological, and echocardiographic characteristics were analyzed in IE HCM patients (n = 34) and in IE HCM reported in literature (n = 84). Patients with nondevice IE (n = 1807) were classified into 3 groups: group 1, HCM with native-valve IE (n = 26); group 2, patients with IEAP indication (n = 696); group 3, patients with no IEAP indication (n = 1085). IE episode and 1-year follow-up data were gathered.One-year mortality in IE HCM was 42% in our study and 22% in the literature. IE was more frequent, although not exclusive, in obstructive HCM (59% and 74%, respectively). Group 1 exhibited more IE predisposing factors than groups 2 and 3 (62% vs 40% vs 50%, P < 0.01), and more previous dental procedures (23% vs 6% vs 8%, P < 0.01). Furthermore, Group 1 experienced a higher incidence of Streptococcus infections than Group 2 (39% vs 22%, P < 0.01) and similar to Group 3 (39% vs 30%, P = 0.34). Overall mortality was similar among groups (42% vs 36% vs 35%, P = 0.64).IE occurs in HCM patients with and without obstruction. Mortality of IE HCM is high but similar to patients with and without IEAP indication. Predisposing factors, previous dental procedures, and streptococcal infection are higher in IE HCM, suggesting that HCM patients could benefit from IEAP.
| S-EPMC4937928 | biostudies-literature
Project description:BackgroundLittle is known about the characteristics and impact of septic shock (SS) on the outcomes of infective endocarditis (IE). We aimed to investigate the characteristics and outcomes of patients with IE presenting with SS and to compare them to those of IE patients with sepsis (Se) and those with neither Se nor SS (no-Se-SS).MethodsThis is a prospective cohort study of 4864 IE patients from 35 Spanish centers (2008 to 2018). Logistic regression analyses were performed to identify risk factors for SS and mortality.ResultsSeptic shock and Se presented in 597 (12.3%) and 559 (11.5%) patients, respectively. Patients with SS were younger and presented significantly higher rates of diabetes, chronic renal and liver disease, transplantation, nosocomial acquisition, Staphylococcus aureus, IE complications, and in-hospital mortality (62.5%, 37.7% for Se and 18.2% for no-Se-SS, P < .001). Staphylococcus aureus (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.34-2.81; P < .001), Gram negative (OR, 2.21; 95% CI, 1.25-3.91; P = .006), nosocomial acquisition (OR, 1.44; 95% CI, 1.07-1.94; P = .015), persistent bacteremia (OR, 1.82; 95% CI, 1.24-2.68; P = .002), acute renal failure (OR, 3.02; 95% CI, 2.28-4.01; P < .001), central nervous system emboli (OR, 1.48; 95% CI, 1.08-2.01; P = .013), and larger vegetation size (OR, 1.01; 95% CI, 1.00-1.02; P. = 020) were associated with a higher risk of developing SS. Charlson score, heart failure, persistent bacteremia, acute renal failure, mechanical ventilation, worsening of liver disease, S aureus, and receiving aminoglycosides within the first 24 hours were associated with higher in-hospital mortality, whereas male sex, native valve IE, and cardiac surgery were associated with lower mortality.ConclusionsSeptic shock is frequent and entails dismal prognosis. Early identification of patients at risk of developing SS and early assessment for cardiac surgery appear as key factors to improve outcomes.
| S-EPMC8232381 | biostudies-literature
Project description:The parasitic helminth Fasciola hepatica (liver fluke) causes economic loss to the livestock industry globally and also causes zoonotic disease. New control strategies such as vaccines are urgently needed, due to the rise of drug resistance in parasite populations. Vaccine development requires a comprehensive understanding of the immunological events during infection. Previous in vivo studies by our group have investigated global differentially expressed genes (DEGs) in ovine peripheral blood mononuclear cells (PBMC) in response to both acute and chronic F. hepatica infection. This work demonstrated that pathways involved in the pathogenesis of ovine fasciolosis included fibrosis, inhibition of macrophage nitric oxide production, and antibody isotype switching, among others. Transcriptomic changes in PBMC populations following F. hepatica infection in cattle, in which the disease phenotype is quite different, have not yet been examined. Using RNA sequencing we investigated gene expression changes in PBMC isolated from 9 non-infected and 11 F. hepatica-experimentally-infected calves immediately before infection, at 1 and at 14 weeks post-infection. Longitudinal time-course comparisons between groups revealed 21 and 1,624 DEGs driven exclusively by F. hepatica infection in cattle at acute and chronic stages, respectively. These results show that fewer DEGs at the acute stage of infection can be identified in cattle, as compared with sheep. In addition, the log2 fold-changes of these DEGs were relatively low (-1 to 3) reflecting the different clinical presentation of F. hepatica infection in cattle. Gene pathways for hepatic fibrosis and hepatic cholestasis along with apoptosis of antigen-presenting cells were enriched at chronic stages. Our results reflect the major differences in the disease phenotype between cattle and sheep and may indicate pathways to target in vaccine development.
| S-EPMC6727689 | biostudies-literature
Project description:Background: Schizophrenia is a serious mental disorder with complicated biological mechanisms. Few studies explore the transcriptional features that are shared in brain tissue and peripheral blood. In the present study, we aimed to explore the biological pathways with similar expression patterns in both peripheral blood mononuclear cells (PBMCs) and brain tissues. Methods: The present study used transcriptomics technology to detect mRNA expression of PBMCs of 10 drug-naïve patients with schizophrenia and 20 healthy controls. Transcriptome data sets of brain tissue of patients with schizophrenia downloaded from public databases were also analyzed in our study. The biological pathways with similar expression patterns in the PBMCs and brain tissues were uncovered by differential expression analysis, weighted gene co-expression network analysis (WGCNA), and pathway analysis. Finally, the expression levels of differential expressed genes (DEGs) were validated by real-time fluorescence quantitative polymerase chain reaction (qPCR) in another 12 drug-naïve patients with schizophrenia and 12 healthy controls. Results: We identified 542 DEGs, 51 DEGs, 732 DEGs, and 104 DEGs in PBMCs, dorsolateral prefrontal cortex, anterior cingulate gyrus, and nucleus accumbent, respectively. Five DEG clusters were recognized as having similar gene expression patterns in PBMCs and brain tissues by WGCNA. The pathway analysis illustrates that these DEG clusters are mainly enriched in several biological pathways that are related to phospholipid metabolism, ribosome signal transduction, and mitochondrial oxidative phosphorylation. The differential significance of PLAAT3, PLAAT4, PLD2, RPS29, RPL30, COX7C, COX7A2, NDUFAF2, and ATP5ME were confirmed by qPCR. Conclusions: This study finds that the pathways associated with phospholipid metabolism, ribosome signal transduction, and energy metabolism have similar expression patterns in PBMCs and brain tissues of patients with schizophrenia. Our results supply a novel insight for revealing the pathogenesis of schizophrenia and might offer a new approach to explore potential biological markers of peripheral blood in schizophrenia.
| S-EPMC8492981 | biostudies-literature
Project description:Detection of lymphocytes that target tumor-specific mutant neoantigens--derived from products encoded by mutated genes in the tumor--is mostly limited to tumor-resident lymphocytes, but whether these lymphocytes often occur in the circulation is unclear. We recently reported that intratumoral expression of the programmed cell death 1 (PD-1) receptor can guide the identification of the patient-specific repertoire of tumor-reactive CD8(+) lymphocytes that reside in the tumor. In view of these findings, we investigated whether PD-1 expression on peripheral blood lymphocytes could be used as a biomarker to detect T cells that target neoantigens. By using a high-throughput personalized screening approach, we identified neoantigen-specific lymphocytes in the peripheral blood of three of four melanoma patients. Despite their low frequency in the circulation, we found that CD8(+)PD-1(+), but not CD8(+)PD-1(-), cell populations had lymphocytes that targeted 3, 3 and 1 unique, patient-specific neoantigens, respectively. We show that neoantigen-specific T cells and gene-engineered lymphocytes expressing neoantigen-specific T cell receptors (TCRs) isolated from peripheral blood recognized autologous tumors. Notably, the tumor-antigen specificities and TCR repertoires of the circulating and tumor-infiltrating CD8(+)PD-1(+) cells appeared similar, implying that the circulating CD8(+)PD-1(+) lymphocytes could provide a window into the tumor-resident antitumor lymphocytes. Thus, expression of PD-1 identifies a diverse and patient-specific antitumor T cell response in peripheral blood, providing a novel noninvasive strategy to develop personalized therapies using neoantigen-reactive lymphocytes or TCRs to treat cancer.
| S-EPMC7446107 | biostudies-literature