scholarly journals Circulating Long Noncoding RNAs Positively Correlate with the Increased Risk, Elevated Severity and Unfavorable Prognosis in the Sepsis Patients

Author(s):  
Jun Yuan ◽  
Limian Cao ◽  
Junjie Bao ◽  
Yutao Zha ◽  
Shi Chen ◽  
...  

Abstract Objective This study aimed to evaluate the correlation of circulating long noncoding RNAs (lncRNAs) expression with disease risk, severity, inflammatory cytokines levels and prognosis in patients with sepsis. Methods Differential expression profiles of lncRNA in the serum of sepsis rats were screened by high-throughput transcriptome sequencing. Homologous lncRNAs in the upregulation group were identified by homology analysis in rats and humans. The expression differences of these homologous lncRNAs in the serum of 176 sepsis patients and 176 healthy controls (HCs) were detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). And inflammatory cytokines levels were detected by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic (ROC) curve was used to verify the diagnostic and prognosis values. Spearman correlation coefficient was used to analyze the correlation between the variables. Follow-up was performed to observe the 28-day mortality. Results Among the screened differentially up-regulated lncRNAs, only two lncRNAs were homologous in rats and humans, which in human named PKN2-antisense RNA 1 (PKN2-AS1) and AC068888.1, respectively. Those two lncRNAs were significantly increased in patients with sepsis compared with those in HCs (P < 0.001), in patients with septic shock compared with those no septic shock (P < 0.001), and in non-survivors compared with survivors (P < 0.001). And those two lncRNAs were positively correlated with sepsis-related organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE) II score, lactate (Lac), c-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in sepsis patients. Likelihood ratio forward stepwise multivariate logistic regression analysis revealed that high lncRNA AC068888.1 expression was an independent risk factor for septic shock (P < 0.001) and unfavorable prognosis (P = 0.006), but high lncRNA PKN2-AS1 expression was only for unfavorable prognosis (P = 0.019). The ROC curve exhibited a significant predictive value for sepsis risk with area under the curve (AUC) values of 0.879 and 0.842, respectively. For predicting septic shock risk, combining lncRNA AC068888.1 with SOFA score and Lac level, the ROC curve analysis significantly improved the predictability (AUC = 0.882). For predicting 28-day death risk, combining those two lncRNAs with SOFA and APACHE II scores, the ROC curve analysis also significantly improved the predictability (AUC = 0.860). The Kaplan–Meier curves indicated that the survival probability was much worse with those two lncRNAs high expression compared to low expression in patients with sepsis (P < 0.001). Conclusion The circulating absolute expression levels of lncRNA PKN2-AS1 and AC068888.1 in the serum may be used for the early diagnosis, clinical severity evaluation and prognosis of sepsis.

2019 ◽  
Vol 26 (5) ◽  
pp. 341-350
Author(s):  
Zhao-Juan Er ◽  
Chun-Fang Yin ◽  
Wen-Jing Wang ◽  
Xue-Jun Chen

This study aimed to examine whether stromal cell-derived factor-1 (SDF-1) or C-X-C chemokine ligand 12 (CXCL12) participates in the development of lumbar disc degeneration, as implicated earlier by the level of CXCL12 correlating with this disease. It enrolled 145 patients with symptomatic lumbar intervertebral disc degeneration (IDD) and 130 asymptomatic healthy controls with no indication of IDD. Radiological assessment of the IDD patients was targeted at the lumbar vertebra region, based on Pfirrmann grade. Degeneration of the multifidus and psoas major muscles was evaluated using Goutallier classification. Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were obtained for assessing the severity of manifestation. The levels of serum CXCL12, IL-6 and TNF-α were determined by ROC curve analysis, resulting in their prognostic value for Pfirrmann grading. Higher levels of serum CXCL12 were found in patients with IDD than in asymptomatic individuals, and were positively related to the Pfirrmann grade as well as multifidus muscle degeneration. Furthermore, serum CXCL12 concentration showed a significant correlation with the VAS and ODI scores. In addition, elevated serum CXCL12 levels were related to serum levels of TNF-α and IL-6. The ROC curve analysis implicated that CXCL12 could function as a biomarker of the early-mediate phase of IDD development. In summary, the serum CXCL12/SDF-1 level is positively related with lumbar IDD and its clinical severity.


2019 ◽  
Author(s):  
Jing Li ◽  
Min Ming ◽  
Yonghong Han

Abstract Background This study aimed to investigate the predictive value of JNK pathway-associated phosphatase (JKAP) level for severe acute pancreatitis (SAP) risk, and its association with disease severity, inflammation and in-hospital mortality in SAP patients. Methods Our study recruited 50 SAP patients, 50 moderate-severe acute pancreatitis (MSAP) patients, 50 mild acute pancreatitis (MAP) patients and 50 healthy controls. And the serum samples were obtained from all acute pancreatitis patients within 24 hours after admission and from health controls at their enrollment to detect JKAP level by enzyme-linked immunosorbent assay. Results JKAP level was decreased in SAP patients compared with healthy controls, MSAP and MAP patients. And receiver operating characteristics (ROC) curve analysis revealed that JKAP could not only distinguish SAP patients from healthy controls (AUC: 0.914, 95%CI: 0.857-0.971), but also differentiate SAP patients from MAP patients (AUC: 0.869, 95%CI: 0.802-0.937) and MSAP patients (AUC: 0.712, 95%CI: 0.610-0.813). In SAP patients, JKAP was negatively correlated with Ranson score, acute physiology and chronic health care evaluation II (APACEH II) score, sequential organ failure assessment (SOFA) score and C-reactive protein (CRP). And lower JKAP level, higher CRP level, Ranson score, APACEH II score and SOFA score were associated with increased in-hospital mortality in SAP patients. Additionally, ROC curve analysis showed that JKAP could predict decreased in-hospital mortality in SAP patients (AUC: 0.720, 95%CI: 0.526-0.914). Conclusions JKAP might serve as a biomarker for disease risk and management for SAP.


2016 ◽  
Vol 311 (3) ◽  
pp. H707-H712 ◽  
Author(s):  
Janina Kitow ◽  
Anselm A. Derda ◽  
Julia Beermann ◽  
Regalla Kumarswarmy ◽  
Angelika Pfanne ◽  
...  

Hypertrophic cardiomyopathy (HCM) is a hereditary heart disease with a high risk for sudden cardiac death in young people. As a subtype, hypertrophic obstructive cardiomyopathy (HOCM) additionally has a left ventricular outflow gradient, showing stronger symptoms and requires a different treatment compared with hypertrophic nonobstructive cardiomyopathy (HNCM). In this study our aim was to investigate the regulation of mitochondrial and cardiac remodeling associated long noncoding RNAs (lncRNAs) in blood of patients affected with HOCM and HNCM. We included 28 HNCM, 57 HOCM, and 26 control inviduals. Already known mitochondrial and cardiac remodeling associated lncRNAs uc004cos.4, uc004coz.1, uc004cov.4, uc011mfi.2, uc022bqw.1, uc022bqs.1, and uc022bqu.1 were amplified in serum of these patients and correlated with clinical parameters. Long noncoding RNAs uc004cov.4 and uc022bqu.1 were significantly increased in patients with HOCM but not in patients with HNCM. With the use of receiver operator characteristic (ROC) curve analysis, lncRNAs uc004cov.4 and uc022bqu.1 were able to identify HOCM patients. In our study we evidenced that the specific mitochondrial long noncoding RNAs uc004cov.4 and uc022bqu.1 were upregulated in patients with HOCM and they were also able to identify HOCM and could be developed as useful clinical biomarkers in the future.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Santos ◽  
S Paula ◽  
I Almeida ◽  
H Santos ◽  
H Miranda ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients (P) with acute heart failure (AHF) are a heterogeneous population. Risk stratification at admission may help predict in-hospital complications and needs. The Get With The Guidelines Heart Failure score (GWTG-HF) predicts in-hospital mortality (M) of P admitted with AHF. ACTION ICU score is validated to estimate the risk of complications requiring ICU care in non-ST elevation acute coronary syndromes. Objective To validate ACTION-ICU score in AHF and to compare ACTION-ICU to GWTG-HF as predictors of in-hospital M (IHM), early M [1-month mortality (1mM)] and 1-month readmission (1mRA), using real-life data. Methods Based on a single-center retrospective study, data collected from P admitted in the Cardiology department with AHF between 2010 and 2017. P without data on previous cardiovascular history or uncompleted clinical data were excluded. Statistical analysis used chi-square, non-parametric tests, logistic regression analysis and ROC curve analysis. Results Among the 300 P admitted with AHF included, mean age was 67.4 ± 12.6 years old and 72.7% were male. Systolic blood pressure (SBP) was 131.2 ± 37.0mmHg, glomerular filtration rate (GFR) was 57.1 ± 23.5ml/min. 35.3% were admitted in Killip-Kimball class (KKC) 4. ACTION-ICU score was 10.4 ± 2.3 and GWTG-HF was 41.7 ± 9.6. Inotropes’ usage was necessary in 32.7% of the P, 11.3% of the P needed non-invasive ventilation (NIV), 8% needed invasive ventilation (IV). IHM rate was 5% and 1mM was 8%. 6.3% of the P were readmitted 1 month after discharge. Older age (p &lt; 0.001), lower SBP (p = 0,035) and need of inotropes (p &lt; 0.001) were predictors of IHM in our population. As expected, patients presenting in KKC 4 had higher IHM (OR 8.13, p &lt; 0.001). Older age (OR 1.06, p = 0.002, CI 1.02-1.10), lower SBP (OR 1.01, p = 0.05, CI 1.00-1.02) and lower left ventricle ejection fraction (LVEF) (OR 1.06, p &lt; 0.001, CI 1.03-1.09) were predictors of need of NIV. None of the variables were predictive of IV. LVEF (OR 0.924, p &lt; 0.001, CI 0.899-0.949), lower SBP (OR 0.80, p &lt; 0.001, CI 0.971-0.988), higher urea (OR 1.01, p &lt; 0.001, CI 1.005-1.018) and lower sodium (OR 0.92, p = 0.002, CI 0.873-0.971) were predictors of inotropes’ usage. Logistic regression showed that GWTG-HF predicted IHM (OR 1.12, p &lt; 0.001, CI 1.05-1.19), 1mM (OR 1.10, p = 1.10, CI 1.04-1.16) and inotropes’s usage (OR 1.06, p &lt; 0.001, CI 1.03-1.10), however it was not predictive of 1mRA, need of IV or NIV. Similarly, ACTION-ICU predicted IHM (OR 1.51, p = 0.02, CI 1.158-1.977), 1mM (OR 1.45, p = 0.002, CI 1.15-1.81) and inotropes’ usage (OR 1.22, p = 0.002, CI 1.08-1.39), but not 1mRA, the need of IV or NIV. ROC curve analysis revealed that GWTG-HF score performed better than ACTION-ICU regarding IHM (AUC 0.774, CI 0.46-0-90 vs AUC 0.731, CI 0.59-0.88) and 1mM (AUC 0.727, CI 0.60-0.85 vs AUC 0.707, CI 0.58-0.84). Conclusion In our population, both scores were able to predict IHM, 1mM and inotropes’s usage.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuichiro Shimoyama ◽  
Osamu Umegaki ◽  
Noriko Kadono ◽  
Toshiaki Minami

Abstract Objective Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. Results Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320).


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