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The novels biomarkers for assessing clinical benefits of continuous renal replacement therapy in pediatric sepsis

ABSTRACT: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Continuous renal replacement therapy (CRRT) is regarded as an adjuvant therapy for critically ill, which removes excess fluids and clear uremic toxins, endotoxins, proteins, and inflammatory mediators efficiently. In patients with sepsis, CRRT has the advantages of maintaining hemodynamic stability, accurate fluid control, and steady acid-base and electrolyte correction. 2020 “Surviving Sepsis Campaign (SSC) international guidelines” for children suggested that CRRT should be considered in hemodynamically unstable septic patients for promoting management of fluid balance and acute kidney injury (AKI).Blood levels of cytokines (such as interleukin-8 [IL-8], tumor necrosis factor -α [TNF-α], IL-10, and IL-6) and endotoxins are often elevated in patients with sepsis. CRRT removing endotoxins and cytokines from septic patients is associated with improved patient outcomes. Our previous multicenter study indicated th

ORGANISM(S): Homo Sapiens

SUBMITTER: Chunxia Wang

PROVIDER: PXD032807 | iProX | Fri Mar 25 00:00:00 GMT 2022

REPOSITORIES: iProX

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The novel biomarkers for assessing clinical benefits of continuous renal replacement therapy in pediatric sepsis: a pilot study.

Cui Yun Y Feng Shuyun S Miao Huijie H Liu Tiantian T Shi Jingyi J Dou Jiaying J Wang Chunxia C Zhang Yucai Y

Clinical proteomics 20230118 1

<h4>Background</h4>Continuous renal replacement therapy (CRRT) has been considered as an adjuvant therapy for sepsis. However, the novel biomarker to evaluate the benefits of CRRT is limited. The aim of this study was to explore the novel biomarkers involved in the impact of CRRT in pediatric sepsis.<h4>Methods</h4>The serum proteomic profiles on the 7th day after CRRT (CRRT 7th day) compared with before CRRT (CRRT 1st day) was determined in 3 children with sepsis as a discovery set. The screene ...[more]

PMID: 36650427

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Project description:Our experiments examined T-lymphocyte numbers and effector-functions in peritoneal contamination and infection (PCI) a mouse model of sepsis. One of our main questions was how T-lymphocytes reconstitute after sepsis-induced lymphopenia. We investigated the quantitative and qualitative recovery of T lymphocytes for 3.5 months after sepsis with or without IL-7 treatment. Sepsis is an immunological dysfunction against pathogens leading to inflammation with massive cytokine production. Simultaneously immunosuppression occurs e.g. lymphopenia, which is a hallmark of sepsis. The resulting immunosuppression is associated with secondary infections, which are often lethal. Moreover sepsis-survivors are burdened with increased morbidity and mortality for several years after the sepsis episode. The duration and clinical consequences of sepsis induced-immunosuppression are currently unknown. More than 50% of T-cells undergo apoptosis shortly after sepsis-induction. However, 8 days after sepsis onset, surviving mice present normal lymphocyte counts. Theoretically, T-cells could reconstitute in two different ways. Firstly, the diminished pool of T-cells is replenished by newly in thymus produced T-cells with new diverse T-cell-receptors (TCRs). Alternatively, remaining T-cells start to proliferate until reaching normal cell count. If this was the case all divided cells shared the same TCRs as primary cells. This could lead to a narrowed TCR diversity within a quantitative normalized T-cell pool and would be an explanation for the long-lasting immune incompetence. To address the question how T-cells recover from lymphopenia we applied next generation sequencing (NGS) to analyse TCR diversity in septic and healthy mice. One group of septic mice received Interleukin-7 (IL-7), an interleukin which regulates T-cell homeostasis and is a promising therapeutically approach for septic patients. 50000 sequences per mouse were analyzed and the three different groups (controls, sepsis, sepsis + IL-7 treatment) compared regarding their diversity. The sequenced raw data (fastq) are uploaded in this library.

Project description:Sepsis is defined as a systemic inflammatory response secondary to a proven or suspected infection. Mechanisms governing this inflammatory response have been shown to be complex and dynamic, involving cross-talking among diverse signaling pathways. However, current knowledge on mechanisms underlying sepsis is far from providing a complete picture of the syndrome, justifying additional efforts that might add to this scenario. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis: the analysis of gene transcription at the genome level potentially avoids results derived from biased assumptions. In this study we investigate whole-genome gene expression profiles of mononuclear cells from survivor and non-survivor septic patients. Blood samples were collected at the time of sepsis diagnosis and seven days later, allowing us to evaluate the role of biological processes or genes possibly involved in patient recovery. Aiming to circumvent, at least partially, the heterogeneity of septic patients we included only patients admitted with sepsis caused by community-acquired pneumonia. Global gene expression profiling allowed us to characterize early sepsis, as compared to healthy individuals. Our results corroborate literature reports on inflammation response in the early stages of sepsis but highlight great heterogeneity in gene expression during sepsis progress. Additionally, global gene expression in the early stage was also able to distinguish sepsis from septic shock and correlated with patient outcome. Differences in oxidative stress seem to be associated with clinical outcome, since significant differences in the expression profile of related genes were observed between survivors and non-survivors at the time of patient enrollment (early sepsis). However, our results substantiate current knowledge supporting that sepsis syndrome development is indeed multifaceted. Although the initial infection of enrolled patients was pneumonia, seven days later gene expression profiles seemed to be characteristic of each patient, common gene expression changes distinguishing survivors from non-survivors. This result could be associated with the underlying health status of each one of them, with complications due to sepsis itself as well as with distinct timing for response to treatment. In this study we investigate whole-genome gene expression profiles of mononuclear cells from survivor (n=5) and non-survivor (n=5) septic patients, as well as from 3 healthy controls. Blood samples were collected at the time of sepsis diagnosis and seven days later, allowing us to evaluate the role of biological processes or genes possibly involved in patient recovery. Aiming to circumvent, at least partially, the heterogeneity of septic patients we included only patients admitted with sepsis caused by community-acquired pneumonia.

Dataset Information

The novels biomarkers for assessing clinical benefits of continuous renal replacement therapy in pediatric sepsis

Publications

The novel biomarkers for assessing clinical benefits of continuous renal replacement therapy in pediatric sepsis: a pilot study.

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