Immune-cell signatures of persistent inflammation-immunosuppression and catabolism syndrome
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PROVIDER: PRJNA901378 | ENA |
REPOSITORIES: ENA
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Project description:Sepsis is a debilitating disease with a worldwide prevalence. An increasing number of patients with sepsis, especially aged patients, suffer from chronic critical illness and develop persistent inflammation-immunosuppression and catabolism syndrome (PICS). Here, we profiled peripheral blood mononuclear cells in four patients with PICS, two patients with acute sepsis, and three healthy controls using single-cell RNA sequencing and systematic analyses. We found that gene expression patterns and developmental routes in distinct immune cell populations exhibited notable differences between patients with PICS, patients with acute sepsis, and healthy controls.
2025-01-23 | GSE217906 | GEO
Project description:We recently proffered that a new syndrome persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has replaced late multiple-organ failure as a predominant phenotype of chronic critical illness. Our goal was to validate this by determining whether severely injured trauma patients with complicated outcomes have evidence of PICS at the genomic level.We performed a secondary analysis of the Inflammation and Host Response to Injury database of adults with severe blunt trauma. Patients were classified into complicated, intermediate, and uncomplicated clinical trajectories. Existing genomic microarray data were compared between cohorts using Ingenuity Pathways Analysis. Epidemiologic data and outcomes were also analyzed between cohorts on admission, Day 7, and Day 14.Complicated patients were older, were sicker, and required increased ventilator days compared with the intermediate/uncomplicated patients. They also had persistent leukocytosis as well as low lymphocyte and albumin levels compared with uncomplicated patients. Total white blood cell leukocyte analysis in complicated patients showed that overall genome-wide expression patterns and those patterns on Days 7 and 14 were more aberrant from control subjects than were patterns from uncomplicated patients. Complicated patients also had significant down-regulation of adaptive immunity and up-regulation of inflammatory genes on Days 7 and 14 (vs. magnitude in fold change compared with control and in magnitude compared with uncomplicated patients). On Day 7, complicated patients had significant changes in functional pathways involved in the suppression of myeloid cell differentiation, increased inflammation, decreased chemotaxis, and defective innate immunity compared with uncomplicated patients and controls. Subset analysis of monocyte, neutrophil, and T-cells supported these findings.Genomic analysis of patients with complicated clinical outcomes exhibit persistent genomic expression changes consistent with defects in the adaptive immune response and increased inflammation. Clinical data showed persistent inflammation, immunosuppression, and protein depletion. Overall, the data support the hypothesis that patients with complicated clinical outcomes are exhibiting PICS.Epidemiologic study, level III.
| S-EPMC4310749 | biostudies-literature
Project description:ObjectivesTo provide an appraisal of the evolving paradigms in the pathophysiology of sepsis and propose the evolution of a new phenotype of critically ill patients, its potential underlying mechanism, and its implications for the future of sepsis management and research.DesignLiterature search using PubMed, MEDLINE, EMBASE, and Google Scholar.Measurements and main resultsSepsis remains one of the most debilitating and expensive illnesses, and its prevalence is not declining. What is changing is our definition(s), its clinical course, and how we manage the septic patient. Once thought to be predominantly a syndrome of over exuberant inflammation, sepsis is now recognized as a syndrome of aberrant host protective immunity. Earlier recognition and compliance with treatment bundles has fortunately led to a decline in multiple organ failure and in-hospital mortality. Unfortunately, more and more sepsis patients, especially the aged, are suffering chronic critical illness, rarely fully recover, and often experience an indolent death. Patients with chronic critical illness often exhibit "a persistent inflammation-immunosuppression and catabolism syndrome," and it is proposed here that this state of persisting inflammation, immunosuppression and catabolism contributes to many of these adverse clinical outcomes. The underlying cause of inflammation-immunosuppression and catabolism syndrome is currently unknown, but there is increasing evidence that altered myelopoiesis, reduced effector T-cell function, and expansion of immature myeloid-derived suppressor cells are all contributory.ConclusionsAlthough newer therapeutic interventions are targeting the inflammatory, the immunosuppressive, and the protein catabolic responses individually, successful treatment of the septic patient with chronic critical illness and persistent inflammation-immunosuppression and catabolism syndrome may require a more complementary approach.
| S-EPMC5243156 | biostudies-literature
Project description:Many patients in intensive care units, especially the elderly, suffer from chronic critical illness and exhibit a new pathophysiological phenotype: persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Most patients with PICS have a constellation of digestive-system symptoms and gut failure. Akkermansia muciniphila (Akk) is a commensal gut bacterium that reduces inflammation, balances immune responses, modulates energy metabolism, and supports gut health. This study investigated the protective effects and underlying mechanisms of live and pasteurized Akk in treating PICS in a mouse model. PICS was induced on day 14 after performing cecal ligation and puncture (CLP) on day 1 and administrating lipopolysaccharide on day 11. Pasteurized or live Akk, or phosphate-buffered saline was administered twice daily by oral gavage for 7 days. Both live and pasteurized Akk attenuated PICS, as evidenced by reduced weight loss, and a reduction in symptoms and serum cytokine/chemokine levels. Liver and intestinal injuries were mitigated, and intestinal barrier integrity improved with Akk administration. Analysis of 16S rRNA amplicon sequences showed that Akk induced significant intestinal microbiota alterations, including increased abundance of Akk, Muribaculaceae, Parabacterbides goldsteinii, and decreased abundance of Escherichia_Shigella and Enterobacteriaceae. Collectively, Akk alleviates PICS by enhancing gut barrier function and reshaped the microbial community.
| S-EPMC9961567 | biostudies-literature
Project description:Persistent inflammation, immunosuppression and catabolism syndrome (PIICS) often occur after critical care. Disseminated intravascular coagulation (DIC) is expected to be associated independently with PIICS development. We retrospectively analyzed 5397 patients admitted to the Hitachi General Hospital emergency and critical care center during four years. We classified PIICS as C-reactive protein > 3.0 mg/dL or albumin < 3.0 g/dL or lymphocyte count < 800/μL on day 14. Prolonged hospital stay (>14 days) without PIICS and early recovery (discharged alive within 14 days) were assigned as non-PIICS. Early death (death within 14 days) was identified. We analyzed the association between the International Society on Thrombosis and Haemostasis overt DIC and PIICS outcomes. Results revealed 488 PIICS, 416 early death and 4493 non-PIICS cases. Analyses showed DIC as associated significantly with mortality, the Barthel index at discharge and PIICS development. Multivariate regression analysis and a generalized structural equation model identified DIC on admission as an independent risk factor for PIICS in surviving patients.
| S-EPMC7464448 | biostudies-literature
Project description:Severe acute pancreatitis (SAP) is a severe disease with a high prevalence and a 3-15% mortality worldwide, and premature activation of zymogen for any reason is the initial factor for the onset of SAP. Gallstone disease and heavy alcohol consumption are the two most common etiologies of SAP. Persistent inflammation, immunosuppression and catabolism syndrome (PICS) is a life-threatening illness, and there are no effective treatments. The relapse state of PICS mainly leads to high mortality due to septic shock or severe trauma, both of which are dangerous and challenging conditions for clinicians. Thus, it is important for medical staff to identify patients at high risk of PICS and to master the prevention and treatment of PICS in patients with SAP. The present review aims to increase the understanding of the pathogenesis of PICS, produce evidence for PICS diagnosis and highlight clinical treatment for PICS in patients with SAP. With this information, clinical workers could implement standardized and integrated measures at an early stage of SAP to stop its progression to PICS.
| S-EPMC10519614 | biostudies-literature
Project description:Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) is a clinical endotype of chronic critical illness. PICS consists of a self-perpetuating cycle of ongoing organ dysfunction, inflammation, and catabolism resulting in sarcopenia, immunosuppression leading to recurrent infections, metabolic derangements, and changes in bone marrow function. There is heterogeneity regarding the definition of PICS. Currently, there are no licensed treatments specifically for PICS. However, findings can be extrapolated from studies in other conditions with similar features to repurpose drugs, and in animal models. Drugs that can restore immune homeostasis by stimulating lymphocyte production could have potential efficacy. Another treatment could be modifying myeloid-derived suppressor cell (MDSC) activation after day 14 when they are immunosuppressive. Drugs such as interleukin (IL)-1 and IL-6 receptor antagonists might reduce persistent inflammation, although they need to be given at specific time points to avoid adverse effects. Antioxidants could treat the oxidative stress caused by mitochondrial dysfunction in PICS. Possible anti-catabolic agents include testosterone, oxandrolone, IGF-1 (insulin-like growth factor-1), bortezomib, and MURF1 (muscle RING-finger protein-1) inhibitors. Nutritional support strategies that could slow PICS progression include ketogenic feeding and probiotics. The field would benefit from a consensus definition of PICS using biologically based cut-off values. Future research should focus on expanding knowledge on underlying pathophysiological mechanisms of PICS to identify and validate other potential endotypes of chronic critical illness and subsequent treatable traits. There is unlikely to be a universal treatment for PICS, and a multimodal, timely, and personalised therapeutic strategy will be needed to improve outcomes for this growing cohort of patients.
| S-EPMC10870139 | biostudies-literature
Project description:Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) is a serious condition after critical care. We examined the efficacy of antithrombin, which may attenuate coagulopathy with the control of inflammation, for PICS among patients with sepsis-induced disseminated intravascular coagulation (DIC). The present study used the inpatient claims database with laboratory findings to identify patients admitted to intensive care units and diagnosed with sepsis and DIC. A composite of the incidence of PICS on day 14 or 14-day mortality as the primary outcome was compared between the antithrombin and control groups using a propensity-score-matched analysis. Secondary outcomes were the incidence of PICS on day 28, 28-day mortality, and in-hospital mortality. A total of 324 well-balanced matched pairs were generated from 1622 patients. The primary outcome did not differ between the antithrombin and control groups (63.9% vs. 68.2%, respectively, p = 0.245). However, the incidences of 28-day and in-hospital mortality were significantly lower in the antithrombin group (16.0% vs. 23.5% and 24.4% vs. 35.8%, respectively). Similar results were obtained in a sensitivity analysis using overlap weighting. Antithrombin did not reduce the occurrence of PICS on day 14 in patients with sepsis-induced DIC; however, it was associated with a better mid-term (day 28) prognosis.
| S-EPMC10253515 | biostudies-literature
Project description:Background: While clinical criteria have been proposed for persistent inflammation, immunosuppression, and catabolism syndrome (PICS) using C-reactive protein (CRP), albumin, and lymphocyte count, there is no substantial basis for their optimal cut-off values. We herein aimed to develop and externally validate clinical criteria for PICS by investigating the optimal cut-off values for these biomarkers using machine-learning approaches and confirmed it with external validation. Methods: To develop criteria, we included ICU patients treated at a tertiary care hospital in Japan between 2018 and 2021 (derivation cohort). We introduced CRP, albumin and lymphocyte counts at around day 14 into six machine-learning models to predict PICS, defined as the compound outcome of the Barthel index (BI) < 70 at hospital discharge and in-hospital death. We incorporated the results of these models to assess the optimal cut-off values for biomarkers. We then developed and externally validated criteria for PICS using a nationwide claims database in Japan (validation cohort). Results: In the derivation cohort, 291 out of 441 patients had BI < 70 or in-hospital death. Based on machine-learning models, the optimal cut-off values for biomarkers to predict them were a CRP of 2.0 mg/dL, albumin of 3.0 g/dL, and a lymphocyte count of 800/μL, with an AUROC of 0.67. In the external validation cohort, 4492 out of 15,302 patients had BI < 70 or in-hospital death. The AUROC of the criteria was 0.71, with sensitivity of 0.71 and specificity of 0.68 to predict PICS. Conclusions: We herein provide a fundamental basis for PICS clinical criteria with CRP >2.0 mg/dL, albumin <3.0 g/dL, and a lymphocyte count <800/μL on day 14. The criteria developed will identify patients with PICS whose long-term mortality and activity of daily living may be poor.
| S-EPMC9571101 | biostudies-literature
Project description:IntroductionPersistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS.MethodsMEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale.ResultsSix papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L-1 higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L-1; P<0.01), a 4.4 g L-1 lower albumin (95% CI 0.5-8.3 g L-1; P<0.01), and a 0.36×109 L-1 lower lymphocyte count (95% CI 0.25-0.47×109 L-1; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly.ConclusionsWhile older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions.Clinical trial registrationInternational Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749).
| S-EPMC11347813 | biostudies-literature