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Developmental Neurorehabilitation Apr 2023The aim of this systematic literature review was to assess the data regarding neuromarkers used to evaluate the impact of cardiovascular surgery on neurodevelopmental...
The aim of this systematic literature review was to assess the data regarding neuromarkers used to evaluate the impact of cardiovascular surgery on neurodevelopmental pattern of children with congenital heart defects. A systematic search was performed on PubMed and Google Scholar databases. Out of 713 publications screened, 10 studies (471 patients) met the inclusion criteria. The included studies were coded on several variables: number and heterogeneity of patients (age, congenital heart defects), exclusion of patients with conditions that predispose to neurological impairment, neuroimaging workup pre- and post-surgery, neurodevelopmental assessment, interventions (part of a different study), and follow-up period. Results were reported according to PRISMA guidelines. Findings include: neuron-specific enolase and brain-derived neurotrophic factor are not reliable neuromarkers, for protein S100B different results were reported, for activin A there is lack of evidence, and glial fibrillary acidic protein could represent a reliable neuromarker for acute brain-injury. Directions for future research are discussed.
Topics: Humans; Child; Biomarkers; Cardiac Surgical Procedures; Heart Defects, Congenital; Brain Injuries; Neuroimaging
PubMed: 36710475
DOI: 10.1080/17518423.2023.2166618 -
Associated genetic variants and potential pathogenic mechanisms of brain arteriovenous malformation.Journal of Neurointerventional Surgery Jun 2023The pathogenic mechanism of brain arteriovenous malformation (bAVM) is poorly understood. A growing body of evidence indicates that genetic factors play crucial roles in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The pathogenic mechanism of brain arteriovenous malformation (bAVM) is poorly understood. A growing body of evidence indicates that genetic factors play crucial roles in bAVM. This study examined genetic variants associated with bAVM through quantitative synthesis and qualitative description of literature.
METHODS
Five databases were searched to gather potentially relevant articles published up to January 2022. STATA 14.0 software was used for statistical analyses. Pooled odds ratios and 95% confidence intervals were calculated with random effect models, and heterogeneity was assessed using the Cochran Q test and quantified with the I test. Sensitivity and publication bias were analyzed to test the robustness of the associations. Variants identified in only one study or with great heterogeneity were not suitable for pooling association analysis, and therefore a qualitative systematic review was performed.
RESULTS
In total, 30 papers were included in a systematic review involving 4709 cases and 7832 controls, where 17 papers were in a meta-analysis. A suggested association of bAVM was observed with rs2071219 in the additive model and rs1333040 in the recessive and additive models. Other variants of genes that could not be analyzed were summarized by qualitative description. These genes were mostly involved in bone morphogenic protein/transforming growth factor beta (BMP/TGF-β), vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR), and RAS-mitogen activated protein kinase (MAPK) signaling and inflammation.
CONCLUSIONS
According to our meta-analysis, rs2071219 and rs1333040 were potentially associated with bAVM. Multiple pathological signaling pathways could affect disease development. Future studies should aim to determine the interaction of candidate genes with environmental risk factors and to elucidate detailed mechanisms of action of variants and genes.1.
Topics: Humans; Intracranial Arteriovenous Malformations; Vascular Endothelial Growth Factor A; Brain; Signal Transduction; Activin Receptors, Type II
PubMed: 35470246
DOI: 10.1136/neurintsurg-2022-018776 -
Human Reproduction Update Sep 2019Adenomyosis commonly occurs with abnormal uterine bleeding (AUB) and is associated with subfertility and a higher miscarriage rate. Recent evidence showed abnormal...
BACKGROUND
Adenomyosis commonly occurs with abnormal uterine bleeding (AUB) and is associated with subfertility and a higher miscarriage rate. Recent evidence showed abnormal vascularization in the endometrium in patients with adenomyosis, suggesting a role of angiogenesis in the pathophysiology of AUB and subfertility in adenomyosis and providing a possible treatment target.
OBJECTIVE AND RATIONALE
We hypothesized that the level of abnormal vascularization and expression of angiogenic markers is increased in the ectopic and eutopic endometrium of adenomyosis patients in comparison with the endometrium of control patients. This was investigated through a search of the literature.
SEARCH METHODS
A systematic search was performed in PubMed and Embase until February 2019. Combinations of terms for angiogenesis and adenomyosis were applied as well as AUB, subfertility or anti-angiogenic therapy. The main search was limited to clinical studies carried out on premenopausal women. Original research articles focusing on markers of angiogenesis in the endometrium of patients with adenomyosis were included. Studies in which no comparison was made to control patients or which were not published in a peer-reviewed journal were excluded. A second search was performed to explore the therapeutic potential of targeting angiogenesis in adenomyosis. This search also included preclinical studies.
OUTCOMES
A total of 20 articles out of 1669 hits met our selection criteria. The mean vascular density (MVD) was studied by quantification of CD31, CD34, von Willebrand Factor (vWF) or factor-VIII-antibody-stained microvessels in seven studies. All these studies reported a significantly increased MVD in ectopic endometrium, and out of the six articles that took it into account, four studies reported a significantly increased MVD in eutopic endometrium compared with control endometrium. Five articles showed a significantly higher vascular endothelial growth factor expression in ectopic endometrium and three articles in eutopic endometrium compared with control endometrium. The vascular and pro-angiogenic markers α-smooth muscle actin, endoglin, S100A13, vimentin, matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, tissue factor (TF), DJ-1, phosphorylated mammalian target of rapamycin, activin A, folli- and myostatin, CD41, SLIT, roundabout 1 (ROBO1), cyclooxygenase-2, lysophosphatidic acid (LPA) 1,4-5, phospho signal transducer and activator of transcription 3 (pSTAT3), interleukin (IL)-6, IL-22 and transforming growth factor-β1 were increased in ectopic endometrium, and the markers S100A13, MMP-2 and -9, TF, follistatin, myostatin, ROBO1, LPA1 and 4-5, pSTAT3, IL-6 and IL-22 were increased in eutopic endometrium, compared with control endometrium. The anti-angiogenic markers E-cadherin, eukaryotic translation initiation factor 3 subunit and gene associated with retinoic-interferon-induced mortality 19 were decreased in ectopic endometrium and IL-10 in eutopic endometrium, compared with control endometrium. The staining level of vWF and two pro-angiogenic markers (NF-κB nuclear p65 and TF) correlated with AUB in patients with adenomyosis. We found no studies that investigated the possible relationship between markers of angiogenesis and subfertility in adenomyosis patients. Nine articles reported on direct or indirect targeting of angiogenesis in adenomyosis-either by testing hormonal therapy or herbal compounds in clinical studies or by testing angiogenesis inhibitors in preclinical studies. However, there are no clinical studies on the effectiveness of such therapy for adenomyosis-related AUB or subfertility.
WIDER IMPLICATIONS
The results are in agreement with our hypothesis that increased angiogenesis is present in the endometrium of patients with adenomyosis compared with the endometrium of control patients. It is likely that increased angiogenesis leads to fragile and more permeable vessels resulting in adenomyosis-related AUB and possibly subfertility. While this association has not sufficiently been studied yet, our results encourage future studies to investigate the exact role of angiogenesis in the etiology of adenomyosis and related AUB or subfertility in women with adenomyosis in order to design curative or preventive therapeutic strategies.
Topics: Adenomyosis; Adult; Angiogenesis Inhibitors; Capillary Permeability; Endometrium; Female; Humans; Infertility, Female; Neovascularization, Pathologic; Uterine Hemorrhage
PubMed: 31504506
DOI: 10.1093/humupd/dmz024