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Project description:Background: Community-acquired pneumonia (CAP) is defined as an acute lung infection involving the alveoli that occurs in a patient without recent health care exposure. A complication of CAP is severe sepsis, a syndrome of infection often accompanied by systemic inflammation and organ dysfunction. The aim of this study was to evaluate mRNA and miRNA in whole blood and to perform an integrative analysis to assess cellular signals that play a role in the pathogenesis of patients with CAP-associated sepsis. Methods: This was a prospective, observational, single-center study of patients transported to the Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University. Patients with CAP-associated sepsis were analyzed. The diagnosis of pneumonia was made according to the clinical findings, including blood samples and chest computed tomography scan, and the diagnosis of sepsis followed the Sepsis-3 guidelines. Results: We included 14 critically ill patients with CAP-associated sepsis and 15 healthy control subjects (HCS). The median ages of the patient group and HCS were 78 and 55 years, and their body mass indexes were 22.8 and 21.7 kg/m2, respectively. All patients were treated at the critical care center, and 11 of the 14 patients received ventilatory management. All patients survived. These 14 patients met the diagnostic criteria of Sepsis-3 and were diagnosed as having CAP-associated sepsis. Of them, 6 patients met the diagnostic criteria for septic shock. RNA sequencing showed the number of genes with up:down (upregulated:downregulated) expression variation (false discovery rate [FDR] <0.05, |log2 fold change| >1.2) to be 1209:1461 for mRNA; 51:21 for microRNA; and 646:1274 for miRNA-targeted mRNA. Canonical pathway analysis using mRNA showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathways and inhibition of the Th1 signaling pathway as well as that using miRNA-targeted mRNAs. Conclusions: Using integrated analysis of mRNA and miRNA, we elucidated for the first time, to our knowledge, that T-cell exhaustion occurred during the acute phase of CAP-associated sepsis and that miRNA regulated Th1 signaling and PD-1 and PD-L1 cancer immunotherapy signaling through the RNA interference action of mRNA.
2025-04-09 | GSE228541 | GEO
Project description:Background: Community-acquired pneumonia (CAP) is defined as an acute lung infection involving the alveoli that occurs in a patient without recent health care exposure. A complication of CAP is severe sepsis, a syndrome of infection often accompanied by systemic inflammation and organ dysfunction. The aim of this study was to evaluate mRNA and miRNA in whole blood and to perform an integrative analysis to assess cellular signals that play a role in the pathogenesis of patients with CAP-associated sepsis. Methods: This was a prospective, observational, single-center study of patients transported to the Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University. Patients with CAP-associated sepsis were analyzed. The diagnosis of pneumonia was made according to the clinical findings, including blood samples and chest computed tomography scan, and the diagnosis of sepsis followed the Sepsis-3 guidelines. Results: We included 14 critically ill patients with CAP-associated sepsis and 15 healthy control subjects (HCS). The median ages of the patient group and HCS were 78 and 55 years, and their body mass indexes were 22.8 and 21.7 kg/m2, respectively. All patients were treated at the critical care center, and 11 of the 14 patients received ventilatory management. All patients survived. These 14 patients met the diagnostic criteria of Sepsis-3 and were diagnosed as having CAP-associated sepsis. Of them, 6 patients met the diagnostic criteria for septic shock. RNA sequencing showed the number of genes with up:down (upregulated:downregulated) expression variation (false discovery rate [FDR] <0.05, |log2 fold change| >1.2) to be 1209:1461 for mRNA; 51:21 for microRNA; and 646:1274 for miRNA-targeted mRNA. Canonical pathway analysis using mRNA showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathways and inhibition of the Th1 signaling pathway as well as that using miRNA-targeted mRNAs. Conclusions: Using integrated analysis of mRNA and miRNA, we elucidated for the first time, to our knowledge, that T-cell exhaustion occurred during the acute phase of CAP-associated sepsis and that miRNA regulated Th1 signaling and PD-1 and PD-L1 cancer immunotherapy signaling through the RNA interference action of mRNA.
2025-04-09 | GSE228540 | GEO
Project description:Integrated analysis of messenger RNA and microRNA in patients with community-acquired pneumonia associated sepsis
| PRJNA950313 | ENA
Project description:Integrated analysis of messenger RNA and microRNA in patients with community-acquired pneumonia associated sepsis (miRNA part)
| PRJNA950316 | ENA
Project description:Integrated analysis of messenger RNA and microRNA in patients with community-acquired pneumonia associated sepsis (mRNA part)
| PRJNA950318 | ENA
Project description:Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP).To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP.We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07-1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50-2.04) and renal disease (OR, 1.57; 95% CI, 1.21-2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52-0.73). Bacteremia (OR, 1.37; 95% CI, 1.05-1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31-1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10-2.49) were associated with severe sepsis CAP.CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.
| S-EPMC4699794 | biostudies-other
Project description:BackgroundLymphopenia is a marker of poor prognosis in patients with community-acquired pneumonia (CAP), yet its impact on outcomes in patients with CAP and sepsis remains unknown. We aim to investigate the impact of lymphopenia on outcomes, risk of intensive care unit (ICU) admission, and mortality in CAP patients with sepsis.MethodsThis was a retrospective, observational study of prospectively collected data from an 800-bed tertiary teaching hospital (2005-2019).ResultsOf the 2203 patients with CAP and sepsis, 1347 (61%) did not have lymphopenia, while 856 (39%) did. When compared with the nonlymphopenic group, patients with sepsis and lymphopenia more frequently required ICU admission (P = .001), had a longer hospital length of stay (P ˂ .001), and presented with a higher rate of in-hospital (P ˂ .001) and 30-day mortality (P = .001). Multivariable analysis showed that C-reactive protein ≥15 mg/dL, lymphopenia, pleural effusion, and acute respiratory distress syndrome within 24 hours of admission were risk factors for ICU admission; age ≥80 years was independently associated with decreased ICU admission. In addition, age ≥80 years, chronic renal disease, chronic neurologic disease, being a nursing home resident, lymphopenia, and pleural effusion were independently associated with increased 30-day mortality, whereas pneumococcal vaccination, diabetes mellitus, and fever were independently associated with reduced 30-day mortality.ConclusionsLymphopenia was independently associated with risk of ICU admission and higher in-hospital and 30-day mortality in patients with CAP and sepsis. Early identification of lymphopenia could help identify septic patients with CAP who require or will shortly require critical care.
| S-EPMC8231373 | biostudies-literature
Project description:Diagnostic potential of circulating cell-free microRNAs for community-acquired pneu-monia and pneumonia-related sepsis
| PRJEB35757 | ENA
Project description:Mechanisms governing the inflammatory response during sepsis involve crosstalk between diverse signaling pathways, but current knowledge provides an incomplete picture of the syndrome. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis. In this study, we investigated whole-genome expression profiles in mononuclear cells from septic patients admitted in intensive care units with community-acquired pneumonia. Blood samples were collected at the time of sepsis diagnosis and seven days later since we aimed to evaluate the role of biological processes or genes possibly involved in patient recovery. Here we provide a detailed description of the study design, including clinical information, experimental methods and procedures regarding data analysis. Metadata corresponding to microarray results deposited in the database Gene Expression Omnibus (GEO) under the accession number GSE48080 are also described in this report. Our dataset allows the identification of genes possibly associated with host defense to infection as well as gene expression patterns associated with patient outcome.
| S-EPMC4535862 | biostudies-literature
Project description:Little is known about risk and prognostic factors in very old patients developing sepsis secondary to community-acquired pneumonia (CAP). Methods: We conducted a retrospective observational study of data prospectively collected at the Hospital Clinic of Barcelona over a 13-year period. Consecutive patients hospitalized with CAP were included if they were very old (≥80 years) and divided into those with and without sepsis for comparison. Sepsis was diagnosed based on the Sepsis-3 criteria. The main clinical outcome was 30-day mortality. Results: Among the 4219 patients hospitalized with CAP during the study period, 1238 (29%) were very old. The prevalence of sepsis in this age group was 71%. Male sex, chronic renal disease, and diabetes mellitus were independent risk factors for sepsis, while antibiotic therapy before admission was independently associated with a lower risk of sepsis. Thirty-day and intensive care unit (ICU) mortality did not differ between patients with and without sepsis. In CAP-sepsis group, chronic renal disease and neurological disease were independent risk factors for 30-day mortality. Conclusion: In very old patients hospitalized with CAP, in-hospital and 1-year mortality rates were increased if they developed sepsis. Antibiotic therapy before hospital admission was associated with a lower risk of sepsis.
| S-EPMC6678833 | biostudies-literature