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Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies.

ABSTRACT: BACKGROUND:Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous studies showed the relationship between Ang-2 level and the risk of mortality in patients with acute respiratory distress syndrome (ARDS). However, the link between circulating Ang-2 and the risk of mortality in patients with ARDS varied in different investigations. RESULTS:We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating Ang-2 and mortality in patients with ARDS. Among the 10 eligible studies, pooled odds ratio (OR) showed that high Ang-2 level contributed to ARDS mortality [OR?=?1.56, 95% confidence interval (CI): 1.30-1.89, I2?=?76.2%]. Stratified analysis revealed that higher circulating Ang-2 was related to a 30% higher risk in the high-quality scores group (OR?=?1.68, 95% CI: 1.33-2.68, I2?=?62.4%). The I2 of the bad compliance group decreased from 76.2% to 8.5%, which suggested that compliance is a significant source of heterogeneity. This association may be blunted by potential bias, although the results was not meaningfully changed by omitting only one study at a time. Further subgroup analysis and meta-regression support that compliance of patients also affects the results significantly, compared with the publication year, follow-up duration, the samples, or population characteristics. CONCLUSION:Participants with higher baseline Ang-2 were at a higher risk for future risk of mortality in patients with ARDS. Higher circulating Ang-2 levels could independently predict the risk of mortality in patients with ARDS. However, further large scale prospective cohorts or even interventional studies are warranted to evaluate the diagnostic power of Ang-2 and its causative role on ARDS outcome. The reviews of this paper are available via the supplemental material section.

SUBMITTER: Li F

PROVIDER: S-EPMC7013116 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies.

Li Fengyuan F Yin Rulan R Guo Qiang Q

Therapeutic advances in respiratory disease 20200101

<h4>Background</h4>Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous studies showed the relationship between Ang-2 level and the risk of mortality in patients with acute respiratory distress syndrome (ARDS). However, the link between circulating Ang-2 and the risk of mortality in patients with ARDS varied in different investigations.<h4>Results</h4>We performed a systematic review a ...[more]

PMID: 32043429

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Project description:BackgroundAcute liver injury in patients with ARDS decreases survival but early stages may be easily missed due to the lack of sufficient biomarkers signalling its onset. Accordingly, we tested in ARDS patients the hypotheses that microRNA-122, the foremost liver-related microRNA (miR), 1) is an sensitive and specific early predictor for potential liver injury and 2) analysed its impact on 30-day-survival.MethodsWe collected clinical data and analysed blood samples from 119 ARDS patients within the first 24 h of ICU admission and from 20 patients undergoing elective abdominal non-liver surgery serving as controls. Total circulating miR was isolated from serum and relative miR-122 expression was measured (using specific probes and spiked-in miR-54), as were liver function and 30-day survival. Acute liver injury was defined as a total bilirubin concentration???3.0 mg/dl, an ALT activity ?350 U/l, and an INR ?2.0.Results30-day survival of the entire ARDS-cohort was 69% but differed between patients with normal liver function (77%) and acute liver injury (19% p?<? 0.001). miR-122 expression was 20fold higher in non-survivors (95%-CI 0.0149-0.0768; p?=?0.001) and almost 4fold greater in survivors (95%-CI: 0.0037-0.0122; p?=?0.005) compared to controls (95%-CI 0.0008-0.0034) and correlated with markers of liver cell integrity/function [ALT (p?<? 0.001, r?=?0.495), AST (p?<? 0.001, r?=?0.537), total bilirubin (p?=?0.025, r?=?0.206), INR (p?=?0.001, r?=?0.308), and GLDH (p?<? 0.001, r?=?0.489)]. miR-122 serum expression discriminated survivors and non-survivors (AUC: 0.78) better than total bilirubin concentration (AUC: 0.66). Multivariable Cox-regression analysis revealed both acute liver injury (HR 7.6, 95%-CI 2.9-19.8, p?<? 0.001) and miR-122 (HR 4.4, 95%-CI 1.2-16.1, p?=?0.02) as independent prognostic factors for 30-day mortality.ConclusionsIncreased miR-122 serum expression is an early and independent risk factor for 30-day mortality in ARDS patients and potentially reveal an acute liver injury earlier than the conventional markers of liver cell integrity.

Project description:OBJECTIVES:Pediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome. DESIGN:Leveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia. SETTING:The derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia. PATIENTS:There were 624 and 640 subjects in the derivation and validation cohorts, respectively. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ? 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ? 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts. CONCLUSIONS:We describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

Dataset Information

Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies.

Publications

Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies.

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