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The Journal of International Medical... Feb 2021Our aim was to assess the accuracy of angiopoietin-2 (Ang-2) as a prognostic marker for acute pancreatitis (AP) with organ failure (OF). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Our aim was to assess the accuracy of angiopoietin-2 (Ang-2) as a prognostic marker for acute pancreatitis (AP) with organ failure (OF).
METHODS
We undertook a systematic search of the PubMed, Cochrane Library, Embase, Chinese Journals Full-text, Wanfang, China Biology Medicine disc, and Weipu databases to identify eligible cohort studies on the predictive value of Ang-2 for AP with OF. The main outcome measures were sensitivity and specificity. The effects were pooled using a bivariate mixed-effects model.
RESULTS
Six articles with seven case-control studies (n = 650) were included. Pooled sensitivity, specificity, and positive and negative likelihood ratios with 95% confidence intervals (CI) for AP with OF were 0.93 (95%CI: 0.75-0.99), 0.85 (95%CI: 0.75-0.92), 6.40 (95%CI: 3.36-12.19), and 0.08 (95%CI: 0.02-0.36), respectively. The area under the summary receiver operating characteristic curve was 0.95 (95%CI: 0.92-0.96), and the diagnostic odds ratio was 83.18 (95%CI: 11.50-623.17). Subgroup analysis showed that admission time of AP onset (< or ≥24 hours) was a source of overall heterogeneity. Sensitivity analysis supported this finding.
CONCLUSION
Ang-2 had high diagnostic accuracy for AP with OF; the best prediction of Ang-2 may be 24 to 72 hours after onset of AP.
Topics: Angiopoietin-2; Biomarkers; Humans; Multiple Organ Failure; Odds Ratio; Pancreatitis; Prognosis; ROC Curve; Severity of Illness Index; Time Factors
PubMed: 33527867
DOI: 10.1177/0300060520986708 -
Disease Markers 2019In this study, we evaluated the relationship between circulating betatrophin levels and obesity. Obesity is a common public health problem that is increasing globally.... (Meta-Analysis)
Meta-Analysis
In this study, we evaluated the relationship between circulating betatrophin levels and obesity. Obesity is a common public health problem that is increasing globally. Betatrophin, a newly identified protein, is predominantly expressed in white and brown fat tissues and in the liver. Growing evidence suggests that betatrophin plays a pivotal role in metabolism, including the synthesis and degradation of lipids in cells, and adipocyte differentiation. Previous studies have assessed the association between circulating betatrophin levels and obesity; however, this relationship remains unclear. Therefore, our study is aimed at examining the impact of betatrophin on obesity using a meta-analysis of the current evidence. We performed a meta-analysis to quantify the relationship between betatrophin levels and obesity. A literature search was conducted through the EMBASE, Web of Science, and MEDLINE databases. Retrieved studies were screened, without any language restrictions to identify relevant literature published up to December 2018. Observational studies, in which the association between circulating concentrations of betatrophin and obesity was evaluated, were considered suitable for the systematic review. Of the 65 manuscripts retrieved, 9 datasets from 6 studies, involving 681 participants, detected an association between circulating betatrophin and obesity. Circulating betatrophin levels of obese subjects were higher than those of nonobese subjects (random - effects weighted mean difference (WMD) = 0.250 g/mL, 95% CI: 0.048-0.451, = 94.8%, = 0.015), yet with significant between-study heterogeneity. This heterogeneity appeared to be modified by glycemic status but not by age, the ELISA kits used, sample source, or body mass index. The high circulating betatrophin concentration may directly increase the risk of obesity in adults. Betatrophin may serve as a therapeutic target for obesity in adults.
Topics: Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Humans; Obesity; Peptide Hormones
PubMed: 31772689
DOI: 10.1155/2019/5096860 -
Thrombosis Journal 2020Onset, development and progression of atherosclerosis are complex multistep processes. Many aspects of atherogenesis are not yet properly known. This study investigates...
BACKGROUND
Onset, development and progression of atherosclerosis are complex multistep processes. Many aspects of atherogenesis are not yet properly known. This study investigates the changes in vasculature that contribute to switching of vascular cells towards atherogenesis, focusing mainly on ageing.
METHODS
Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving atherogenesis, vascular homeostasis, aging, gene expression, signaling pathways, angiogenesis, vascular development, vascular cell differentiation and maintenance, vascular stem cells, endothelial and vascular smooth muscle cells.
RESULTS
Atherogenesis is a complex multistep process that unfolds in a sequence. It is caused by alterations in: epigenetics and genetics, signaling pathways, cell circuitry, genome stability, heterotypic interactions between multiple cell types and pathologic alterations in vascular microenvironment. Such alterations involve pathological changes in: Shh, Wnt, NOTCH signaling pathways, TGF beta, VEGF, FGF, IGF 1, HGF, AKT/PI3K/ mTOR pathways, EGF, FOXO, CREB, PTEN, several apoptotic pathways, ET - 1, NF-κB, TNF alpha, angiopoietin, EGFR, Bcl - 2, NGF, BDNF, neurotrophins, growth factors, several signaling proteins, MAPK, IFN, TFs, NOs, serum cholesterol, LDL, ephrin, its receptor pathway, HoxA5, Klf3, Klf4, BMPs, TGFs and others.This disruption in vascular homeostasis at cellular, genetic and epigenetic level is involved in switching of the vascular cells towards atherogenesis. All these factors working in pathologic manner, contribute to the development and progression of atherosclerosis.
CONCLUSION
The development of atherosclerosis involves the switching of gene expression towards pro-atherogenic genes. This happens because of pathologic alterations in vascular homeostasis. When pathologic alterations in epigenetics, genetics, regulatory genes, microenvironment and vascular cell biology accumulate beyond a specific threshold, then the disease begins to express itself phenotypically. The process of biological ageing is one of the most significant factors in this aspect as it is also involved in the decline in homeostasis, maintenance and integrity.The process of atherogenesis unfolds sequentially (step by step) in an interconnected loop of pathologic changes in vascular biology. Such changes are involved in 'switching' of vascular cells towards atherosclerosis.
PubMed: 33132762
DOI: 10.1186/s12959-020-00240-z -
Critical Care (London, England) May 2020Heterogeneity of acute respiratory distress syndrome (ARDS) could be reduced by identification of biomarker-based phenotypes. The set of ARDS biomarkers to prospectively...
BACKGROUND
Heterogeneity of acute respiratory distress syndrome (ARDS) could be reduced by identification of biomarker-based phenotypes. The set of ARDS biomarkers to prospectively define these phenotypes remains to be established.
OBJECTIVE
To provide an overview of the biomarkers that were multivariately associated with ARDS development or mortality.
DATA SOURCES
We performed a systematic search in Embase, MEDLINE, Web of Science, Cochrane CENTRAL, and Google Scholar from inception until 6 March 2020.
STUDY SELECTION
Studies assessing biomarkers for ARDS development in critically ill patients at risk for ARDS and mortality due to ARDS adjusted in multivariate analyses were included.
DATA EXTRACTION AND SYNTHESIS
We included 35 studies for ARDS development (10,667 patients at risk for ARDS) and 53 for ARDS mortality (15,344 patients with ARDS). These studies were too heterogeneous to be used in a meta-analysis, as time until outcome and the variables used in the multivariate analyses varied widely between studies. After qualitative inspection, high plasma levels of angiopoeitin-2 and receptor for advanced glycation end products (RAGE) were associated with an increased risk of ARDS development. None of the biomarkers (plasma angiopoeitin-2, C-reactive protein, interleukin-8, RAGE, surfactant protein D, and Von Willebrand factor) was clearly associated with mortality.
CONCLUSIONS
Biomarker data reporting and variables used in multivariate analyses differed greatly between studies. Angiopoeitin-2 and RAGE in plasma were positively associated with increased risk of ARDS development. None of the biomarkers independently predicted mortality. Therefore, we suggested to structurally investigate a combination of biomarkers and clinical parameters in order to find more homogeneous ARDS phenotypes.
PROSPERO IDENTIFIER
PROSPERO, CRD42017078957.
Topics: Angiopoietin-2; Antigens, Neoplasm; Biomarkers; Humans; Mitogen-Activated Protein Kinases; Multivariate Analysis; Respiratory Distress Syndrome
PubMed: 32448370
DOI: 10.1186/s13054-020-02913-7 -
Orphanet Journal of Rare Diseases Oct 2020Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAEnCI) is associated with skin swellings, abdominal attacks, and the risk of asphyxia due to upper airway...
BACKGROUND
Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAEnCI) is associated with skin swellings, abdominal attacks, and the risk of asphyxia due to upper airway obstruction. Several different gene mutations linked to the HAE phenotype have been identified. Our aim was to qualitatively assess and describe the clinical differentiators of these genetically identified HAEnCI types. To achieve this, we performed a systematic literature review of patients with angioedema symptoms and a genetically confirmed diagnosis of an HAEnCI type.
RESULTS
A systematic literature search, conducted in March 2020, returned 132 records, 43 of which describe patients with symptoms of angioedema and a genetically confirmed diagnosis of an HAEnCI type. Overall, this included 602 patient cases from 220 families. HAEnCI with a mutation in the coagulation factor XII gene (F12) (HAE-FXII) was diagnosed in 446 patients from 185 families (male:female ratio = 1:10). Estrogens (oral contraceptives, hormonal replacement therapy, and pregnancy) negatively impacted the course of disease in most female patients (252 of 277). Asphyxia occurred in 2 of 446 patients. On-demand and/or long-term prophylaxis treatment included C1-INH concentrates, icatibant, progestins, and tranexamic acid. HAEnCI with a specific mutation in the plasminogen gene (HAE-PLG) was diagnosed in 146 patients from 33 families (male:female ratio = 1:3). Estrogens had a negative influence on the course of disease in the minority of female patients (14 of 62). Tongue swelling was an important clinical feature. Asphyxia occurred in 3 of 146 patients. On-demand treatment with icatibant and C1-INH concentrate and long-term prophylaxis with progestins and tranexamic acid were effective. HAEnCI with a specific mutation in the angiopoietin-1 gene (HAE-ANGPT1) was diagnosed in 4 patients from 1 family and HAEnCI with a specific mutation in the kininogen-1 gene (HAE-KNG1) in 6 patients from 1 family.
CONCLUSIONS
A number of clinical differentiators for the different types of HAEnCI have been identified which may support clinicians to narrow down the correct diagnosis of HAEnCI prior to genetic testing and thereby guide appropriate treatment and management decisions. However, confirmation of the causative gene mutation by genetic testing will always be required.
Topics: Angioedema; Angioedemas, Hereditary; Complement C1 Inhibitor Protein; Factor XII; Female; Humans; Male; Mutation; Phenotype; Pregnancy
PubMed: 33059692
DOI: 10.1186/s13023-020-01570-x -
Journal of Cerebral Blood Flow and... Dec 2019Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may... (Meta-Analysis)
Meta-Analysis
Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may therefore have therapeutic benefit for ischaemic stroke. This systematic review assessed whether upregulating angiopoietin-1 improved outcomes in rodent models of ischaemic stroke. Random-effects models quantified the effect of angiopoietin-1 upregulation on stroke severity in terms of the size of cerebral infarction and the extent of blood-brain barrier permeability. Eleven studies utilising rat and mouse models of ischaemic stroke fulfilled the inclusion criteria. Meta-analyses demonstrated that angiopoietin-1 upregulation significantly reduced cerebral infarction size (standardised mean difference: -3.02; 95% confidence intervals: -4.41, -1.63; < 0.001; = 171 animals) and improved blood-brain barrier integrity (standardized mean difference: -2.02; 95% confidence intervals: -3.27, -0.77; = 0.002; = 129 animals). Subgroup analyses demonstrated that angiopoietin-1 upregulation improved outcomes in models of transient, not permanent cerebral ischaemia. Six studies assessed the effect of angiopoietin-1 upregulation on neurological function; however, inter-study heterogeneity prevented meta-analysis. In conclusion, published rodent data suggest that angiopoietin-1 upregulation improves outcome following temporary cerebral ischaemia by reducing cerebral infarction size and improving blood-brain barrier integrity. Additional research is required to examine the effect of angiopoietin-1 upregulation on neurological function during stroke recovery and investigate the benefit and risks in patients.
Topics: Angiopoietin-1; Animals; Blood-Brain Barrier; Cerebral Infarction; Disease Models, Animal; Humans; Mice; Rats; Stroke; Up-Regulation
PubMed: 31581897
DOI: 10.1177/0271678X19876876