Monocyte Trajectories Endotypes Are Associated With Worsening in Septic Patients.
Ontology highlight
ABSTRACT:
SUBMITTER: Bodinier M
PROVIDER: S-EPMC8667763 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Sepsis is characterized by dynamic changes of the immune system resulting in deregulated inflammation and failure of homoeostasis and can escalate to septic shock. Circulating monocytes and other innate immune cells are among the first ones to recognize and clear pathogens. Monocytes have an important role in sepsis and septic shock and have been studied as potential diagnostic markers. In total, forty-two patients with septic shock were recruited and blood samples obtained within first 12 hours of ICU admission. We showed that frequency of classical and intermediate monocytes assessed at the time of admission to the intensive care unit are significantly distinct in patients with septic shock who survived longer that five days from those who died. These parameters correlate significantly with differences in serum levels of inflammatory cytokines MCP-1, IL-6, IL-8, IL-10, and IL-18, and with the proportion of helper and cytotoxic T cells. The described changes in frequency of monocyte subsets and their activation status may predict short-term septic shock survival and help with fast identification of the group of vulnerable patients, who may profit from tailored therapy.
| S-EPMC7686971 | biostudies-literature
Project description:The purpose of this study was to determine the potential differential effect of sepsis on innate versus adaptive immune effector cells by examining RNA expression in monocyte/macrophages and CD4 and CD8 T cells respectively using next generation sequencing.
2019-07-29 | GSE133822 | GEO
Project description:BackgroundWhile point-of-care ultrasound (POCUS) has been used to track worsening COVID-19 disease it is unclear if there are dynamic differences between severity trajectories.MethodsWe studied 12-lung zone protocol scans from 244 participants [with repeat scans obtained in 3 days (N = 114), 7 days (N = 53), and weekly (N = 9)] ≥ 18 years of age hospitalized for COVID-19 pneumonia. Differences in mean lung ultrasound (LUS) scores and percent of lung fields with A-lines over time were compared between peak severity levels (as defined by the WHO clinical progression scale) using linear mixed-effects models.ResultsMean LUS scores were elevated by 0.19 (p = 0.035) and A-lines were present in 14.7% fewer lung fields (p = 0.02) among those with ICU-level or fatal peak illness compared to less severe hospitalized illness, regardless of duration of illness. There were no differences between severity groups in the trajectories of mean LUS score 0.19 (p = 0.66) or percent A-lines (p = 0.40).DiscussionOur results do not support the use of serial LUS scans to monitor COVID-19 disease progression among hospitalized adults.
| S-EPMC9720255 | biostudies-literature
Project description:Background Sepsis causes a high rate of mortality and long-term morbidity, associated with an imbalance of innate immunity against infections and inflammation. Obesity and diabetes increase the risk for disease severity. Monocyte dysfunction plays a major role and justify further investigations. Objective To investigate the distribution and inflammatory phenotypes in circulating monocyte subsets in patients manifesting with sepsis including septic shock with and without obesity and diabetes. Methods A total of 235 blood samples were tested from critically ill adult patients registered at the intensive care unit (ICU). The cohorts were divided into non-diabetic groups with or without obesity and diabetic groups with or without obesity, suffering from sepsis or septic shock. We determined frequencies of total monocytes and of monocyte subsets in the circulation and density expression levels of functional markers, including CD14, CD16, HLA-DR, CD33, CD163, CD206, and arginase-1 by flow cytometric analysis. Results When progressing to septic shock in non-diabetic and diabetic patients, the percentages of total monocytes among the leukocyte population and of CD33+ and CD14+ monocytes among the monocyte population were consistently down-regulated compared to non-sepsis in non-diabetic and diabetic patients, respectively. Non-diabetic sepsis patients further presented with decreased CD33 and up-regulated CD163 expression density, which was absent in diabetic patients. We subsequently addressed obesity-related changes of monocytes in non-diabetic and diabetic septic patients. Obese septic patients with diabetes were unique in displaying increased monocytic CD16 and CD163 expression. However, obese septic patients without diabetes solely presented with lower amounts of non-classical monocytes. Body mass index (BMI) dependent changes were restricted to diabetic septic patients, with a significantly higher diminution of the classical monocyte subset and concomitantly increased CD16 expression densities. Conclusion Distribution and phenotypes of monocyte subsets were differentially modulated in critically ill patients with and without metabolic disease when progressing to sepsis or septic shock. Only diabetic septic patients displayed decline of classical monocytes and increase of CD16 expression densities. Therefore, diabetes but not obesity appears to promote the inflammatory phenotype of circulating monocytes in critically ill patients.
| S-EPMC9849690 | biostudies-literature
Project description:Clinical course and mortality in septic patients with low disease severity remain poorly understood and is worth further investigation. We enrolled septic patients admitted to intensive care units (ICUs) between 2010 and 2014 with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ?15. We sought to determine their clinical trajectories and causes of death, and to analyze risk factors associated with in-hospital mortality. A total of 352 patients were included, of whom 89 (25%) did not survive to hospital discharge, at a rate higher than predicted (<21%) by the APACHE II score. Approximately one third (31/89) of non-survivors succumbed to index sepsis; however, more patients (34/89) died of subsequent sepsis. New-onset ICU sepsis developed in 99 (28%) patients and was an independent risk factor for mortality. In addition, septic patients with comorbid malignancy or index infection acquired in the hospital settings were more likely to have in-hospital mortality than those without. In conclusion, septic patients with low APACHE II scores were at a higher mortality risk than expected, and subsequent sepsis rather than index sepsis was the primary cause of death. This study provides insight into unexpected clinical trajectories and outcomes of septic patients with low disease severity at ICU admission and highlights the need for more research and clinical attention in this patient population.
| S-EPMC6678558 | biostudies-literature
Project description:BackgroundAging-related changes in platelet and monocyte interactions may contribute to adverse outcomes in sepsis but remain relatively unexamined. We hypothesized that differential platelet-monocyte aggregate (PMA) formation in older septic patients alters inflammatory responses and mortality.MethodsWe prospectively studied 113 septic adults admitted to the intensive care unit with severe sepsis or septic shock. Patients were dichotomized a priori into one of two groups: older (age ? 65 years, n = 28) and younger (age < 65 years, n = 85). PMA levels were measured in whole blood via flow cytometry within 24 hours of admission. Plasma levels of IL-6 and IL-8, proinflammatory cytokines produced by monocytes upon PMA formation, were determined by commercial assays. Patients were followed for the primary outcome of 28-day, all-cause mortality.ResultsElevated PMA levels were associated with an increased risk of mortality in older septic patients (hazard ratio for mortality 5.64, 95% confidence interval 0.64-49.61). This association remained after adjusting for potential confounding variables in multivariate regression. Receiver operating curve analyses demonstrated that PMA levels greater than or equal to 8.43% best predicted 28-day mortality in older septic patients (area under the receiver operating curve 0.82). Plasma IL-6 and IL-8 levels were also significantly higher in older nonsurvivors. In younger patients, neither PMA levels nor plasma monokines were significantly associated with mortality.ConclusionsIncreased PMA formation, and associated proinflammatory monokine synthesis, predicts mortality in older septic patients. Although larger studies are needed, our findings suggest that heightened PMA formation in older septic patients may contribute to injurious inflammatory responses and an increased risk of mortality.
| S-EPMC4366600 | biostudies-literature
Project description:Sepsis is characterized as life-threatening organ dysfunction caused by a dysregulated host immune response to infection. The purpose of this investigation was to determine the differential effect of sepsis on innate versus adaptive immunity, in humans, by examining RNA expression in specific immune cell subsets, including monocytes/macrophages and CD4 and CD8 T cells. A second aim was to determine immunosuppressive mechanisms operative in sepsis that might be amenable to immunotherapy. Finally, we examined RNA expression in peripheral cells from critically ill nonseptic patients and from cancer patients to compare the unique immune response in these disorders with that occurring in sepsis. Monocytes, CD4 T cells, and CD8 T cells from septic patients, critically ill nonseptic patients, patients with metastatic colon cancer, and healthy controls were analyzed by RNA sequencing. Sepsis induced a marked phenotypic shift toward downregulation of multiple immune response pathways in monocytes suggesting that impaired innate immunity may be fundamental to the immunosuppression that characterizes the disorder. In the sepsis cohort, there was a much more pronounced effect on gene transcription in CD4 T cells than in CD8 T cells. Potential mediators of sepsis-induced immunosuppression included Arg-1, SOCS-1, and SOCS-3, which were highly upregulated in multiple cell types. Multiple negative costimulatory molecules, including TIGIT, Lag-3, PD-1, and CTLA-4, were also highly upregulated in sepsis. Although cancer had much more profound effects on gene transcription in CD8 T cells, common immunosuppressive mechanisms were present in all disorders, suggesting that immunoadjuvant therapies that are effective in one disease may also be efficacious in the others.
| S-EPMC6761013 | biostudies-literature
Project description:Background: Characterization of coronavirus disease 2019 (COVID-19) endotypes may help explain variable clinical presentations and response to treatments. While risk factors for COVID-19 have been described, COVID-19 endotypes have not been elucidated. Objectives: We sought to identify and describe COVID-19 endotypes of hospitalized patients. Methods: Consensus clustering (using the ensemble method) of patient age and laboratory values during admission identified endotypes. We analyzed data from 528 patients with COVID-19 who were admitted to telemetry capable beds at Columbia University Irving Medical Center and discharged between March 12 to July 15, 2020. Results: Four unique endotypes were identified and described by laboratory values, demographics, outcomes, and treatments. Endotypes 1 and 2 were comprised of low numbers of intubated patients (1 and 6%) and exhibited low mortality (1 and 6%), whereas endotypes 3 and 4 included high numbers of intubated patients (72 and 85%) with elevated mortality (21 and 43%). Endotypes 2 and 4 had the most comorbidities. Endotype 1 patients had low levels of inflammatory markers (ferritin, IL-6, CRP, LDH), low infectious markers (WBC, procalcitonin), and low degree of coagulopathy (PTT, PT), while endotype 4 had higher levels of those markers. Conclusions: Four unique endotypes of hospitalized patients with COVID-19 were identified, which segregated patients based on inflammatory markers, infectious markers, evidence of end-organ dysfunction, comorbidities, and outcomes. High comorbidities did not associate with poor outcome endotypes. Further work is needed to validate these endotypes in other cohorts and to study endotype differences to treatment responses.
| S-EPMC8632028 | biostudies-literature
Project description:BackgroundSeptic shock has a high incidence and mortality rate in Intensive Care Units (ICUs). Earlier intravenous fluid resuscitation can significantly improve outcomes in septic patients but easily leads to fluid overload (FO), which is associated with poor clinical outcomes. A single point value of fluid cannot provide enough fluid information. The aim of this study was to investigate the impact of fluid balance (FB) latent trajectories on clinical outcomes in septic patients.MethodsPatients were diagnosed with septic shock during the first 48 h, and sequential fluid data for the first 3 days of ICU admission were included. A group-based trajectory model (GBTM) which is designed to identify groups of individuals following similar developmental trajectories was used to identify latent subgroups of individuals following a similar progression of FB. The primary outcomes were hospital mortality, organ dysfunction, major adverse kidney events (MAKE) and severe respiratory adverse events (SRAE). We used multivariable Cox or logistic regression analysis to assess the association between FB trajectories and clinical outcomes.ResultsNine hundred eighty-six patients met the inclusion criteria and were assigned to GBTM analysis, and three latent FB trajectories were detected. 64 (6.5%), 841 (85.3%), and 81 (8.2%) patients were identified to have decreased, low, and high FB, respectively. Compared with low FB, high FB was associated with increased hospital mortality [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.22-2.17], organ dysfunction [odds ratio (OR) 2.18, 95% CI 1.22-3.42], MAKE (OR 1.80, 95% CI 1.04-2.63) and SRAE (OR 2.33, 95% CI 1.46-3.71), and decreasing FB was significantly associated with decreased MAKE (OR 0.46, 95% CI 0.29-0.79) after adjustment for potential covariates.ConclusionLatent subgroups of septic patients followed a similar FB progression. These latent fluid trajectories were associated with clinical outcomes. The decreasing FB trajectory was associated with a decreased risk of hospital mortality and MAKE.
| S-EPMC8258941 | biostudies-literature
Project description:Nowadays, there is no gold standard of sepsis diagnosis, thus there is a challenge to differentiate between shock septic and non-septic shock following a surgery, since patients with both conditions show similar signs and symptoms. In this sense, to get a quick and accurate diagnosis of septic shock is required to allow an immediate and specific treatment for this condition. In this work, we have evaluated the expression profile by microarray analysis from post-surgical septic shock and non-septic shock patients with the aim of proposing a candidate set genes as gold standard to help in distinguishing both conditions.
2020-08-16 | GSE131761 | GEO