Evaluation of a combination “lymphocyte apoptosis model” to predict survival of sepsis patients in an intensive care unit

Zhong, Wenhong; Deng, Yiyu; Chen, Chunbo; Wang, Qiaosheng; Zhou, Mi; Liu, Xusheng; Sun, Cheng; Zeng, Hongke

doi:10.1186/s12871-018-0535-3

Cited by 17 publications

(34 citation statements)

References 44 publications

(40 reference statements)

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“…Figure 1 shows the scheme of the systematic review. A total of 3,397 articles were screened by title and abstract in the databases analysed (485 in MEDLINE, 1,254 in Scopus and 1,658 in EMBASE), and 44 articles were studied for full‐text analysis 15‐58 . Of these, 12 were excluded because not all the patients were diagnosed with sepsis, 15‐26 seven did not develop a predictive model, 27‐33 in four the outcome to be predicted was not mortality, 34‐37 in another four they did not use their own data, 38‐41 two evaluated only one specific microorganism and not sepsis in general, 42,43 and one applied Machine Learning techniques, 44 which were not considered in this review.…”

Section: Resultsmentioning

confidence: 99%

A critical appraisal of the prognostic predictive models for patients with sepsis: Which model can be applied in clinical practice?

et al. 2021

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Background: Sepsis is associated with high mortality and predictive models can help in clinical decision-making. The objective of this study was to carry out a systematic review of these models. Methods:In 2019, we conducted a systematic review in MEDLINE and EMBASE (CDR42018111121:PROSPERO) of articles that developed predictive models for mortality in septic patients (inclusion criteria). We followed the CHARMS recommendations (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies), extracting the information from its 11 domains (Source of data, Participants, etc). We determined the risk of bias and applicability (participants, outcome, predictors and analysis) through PROBAST (Prediction model Risk Of Bias ASsessment Tool).Results: A total of 14 studies were included. In the CHARMS extraction, the models found showed great variability in its 11 domains. Regarding the PROBAST checklist, only one article had an unclear risk of bias as it did not indicate how missing data were handled while the others all had a high risk of bias. This was mainly due to the statistical analysis (inadequate sample size, handling of continuous predictors, missing data and selection of predictors), since 13 studies had a high risk of bias. Applicability was satisfactory in six articles. Most of the models integrate predictors from routine clinical practice. Discrimination and calibration were assessed for almost all the models, with the area under the ROC curve ranging from 0.59 to 0.955 and no lack of calibration. Only three models were externally validated and their maximum discrimination values in the derivation were from 0.712 and 0.84. One of them (Osborn) had undergone multiple validation studies.Discussion: Despite most of the studies showing a high risk of bias, we very cautiously recommend applying the Osborn model, as this has been externally validated various times.

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Section: Resultsmentioning

confidence: 99%

A critical appraisal of the prognostic predictive models for patients with sepsis: Which model can be applied in clinical practice?

et al. 2021

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“…Further analyses will also be needed to delineate if the association of total caspases-3 and -9 with sepsis or mortality, might actually reflect an active or cleaved form induction. Assessing a “lymphocyte apoptosis model”, higher lymphocyte apoptotic percentages and lower HLA-DR expression independently predicted mortality in septic patients 56 . Moving the sepsis field onwards, this multicenter study’s findings could be taken into consideration and open up the way for future research on apoptotic/antiapoptotic biomarkers implicated in sepsis outcome.…”

Section: Discussionmentioning

confidence: 99%

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis

Miliaraki

Briassoulis

Ilia

et al. 2021

Sci Rep

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Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases’ responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.

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“…It has been estimated that in 2017, the percentage of admissions to the ICU caused by sepsis is ~25% and is associated with a mortality rate >50% worldwide (2,4). Although the precise pathophysiology of sepsis remains unclear, increasing evidence has indicated that it may move from an early hyper-inflammatory phase characterized by systemic inflammation induced by the excessive release of pro-inflammatory factors, followed by a late immuno-suppressive phase, characterized by the apoptosis of immune cells (including monocytes and lymphocytes) (5,6). Furthermore, apoptosis that occurs in the cells of tissues in the site of primary infection during sepsis can result in microvascular dysfunction, which subsequently leads to organ failure (7,8).…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA‑HOTAIR promotes the progression of sepsis by acting as a sponge of miR‑211 to induce IL‑6R expression

Chen

Zhou

et al. 2019

Exp Ther Med

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Sepsis remains the primary cause of death in intensive care units and multiple long non-coding RNAs (lncRNAs) have been demonstrated to be dysregulated in samples of patients with sepsis. However, whether lncRNA-HOTAIR is involved in the etiology of sepsis remains unclear. The aim of the present study was to investigate the role of HOTAIR in sepsis and to reveal the associated mechanisms. A bioinformatics analysis and dual-luciferase reporter assay was performed to evaluate the interaction between HOTAIR and miR-211, as well as miR-211 and IL-6R. An animal model of sepsis was established in mice via cecal ligation and puncture. Interferon (IFN)-γ, interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, IL-1β, IL-6 receptor (R), microRNA (miR)-211 and HOTAIR expression was measured using reverse transcription-quantitative PCR. Cellular proliferation and apoptosis of monocytes were assessed using cell counting kit-8 assay and flow cytometry, respectively. miR-211 was revealed to be targeted by HOTAIR and IL-6R. The expression of IFN-γ, IL-6, IL-17, TNF-α, IL-1β, IL-6R and HOTAIR was significantly upregulated in the septic mice, whereas miR-211 expression was downregulated. The overexpression of hox transcript antisense RNA (HOTAIR) and knockdown of miR-211 were associated with an increased expression of IFN-γ, IL-6, IL-17, TNF-α, IL-1β and IL-6R in monocytes, while the overexpression of miR-211 exhibited the opposite effect. HOTAIR overexpression and miR-211 knockdown significantly inhibited cellular proliferation and promoted monocyte apoptosis, whereas the overexpression of miR-211 exhibited the opposite effects in monocytes. Therefore, HOTAIR may promote the progression of sepsis by indirectly regulating the expression of IL-6R via miR-211.

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Evaluation of a combination “lymphocyte apoptosis model” to predict survival of sepsis patients in an intensive care unit

Cited by 17 publications

References 44 publications

A critical appraisal of the prognostic predictive models for patients with sepsis: Which model can be applied in clinical practice?

A critical appraisal of the prognostic predictive models for patients with sepsis: Which model can be applied in clinical practice?

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis

Long non‑coding RNA‑HOTAIR promotes the progression of sepsis by acting as a sponge of miR‑211 to induce IL‑6R expression

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