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Environmental Health and Preventive... Nov 2017The p.R4810K and other rare variants of ring finger protein 213 gene (RNF213) were illustrated as susceptibility variants for moyamoya (MMD) and non-moyamoya... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The p.R4810K and other rare variants of ring finger protein 213 gene (RNF213) were illustrated as susceptibility variants for moyamoya (MMD) and non-moyamoya intracranial artery stenosis/occlusion disease (ICASO) recently. However, the effect sizes of p.R4810K were in great discrepancy even in studies of the same ethnic population and firm conclusions of other rare variants have been elusive given the small sample sizes and lack of replication. Thus, we performed this study to quantitatively evaluate whether or to what extent the rare variants of RNF213 contribute to MMD and ICASO in different populations.
METHODS
A systematic search of PubMed, EMBASE, ISI web of science, CNKI, and WANFANG DATA was conducted up to 5 September 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effect models based on the between-study heterogeneity. The subgroup analyses were performed by the ethnicity and family history. Sensitivity and publication bias analysis were performed to test the robustness of associations. All the statistical analyses were conduct using STATA 12.0.
RESULTS
Twenty studies including 2353 MMD cases and 5488 controls and 11 studies including 1778 ICASO cases and 3140 controls were included in this study. Pooled ORs indicated that RNF213 p.R4810K significantly increased MMD and ICASO risk in East Asians with great effect sizes of discrepancy (dominant model: odds ratios 184.04, 109.77, and 31.53 and 10.07, 28.52, and 5.59 for MMD and ICASO, respectively, in Japan, Korea, and China). It significantly increased familial MMD risk in Japan, Korea, and China with 5 ~ 36 times larger effect sizes than that for sporadic ones in each country (dominant model ORs 1802.44, 512.42, 1109.02 and 134.35, 99.82, and 30.52, respectively, for familial and sporadic cases). The effect sizes of RNF213 p.R4810K to sporadic MMD were 3 ~ 4 times larger in Japan and Korea than those in China. RNF213 p.R4810K also increased the ICASO risk in Japan and Korea with 2 ~ 4 times larger effect sizes than that in China (dominant model ORs 10.71, 28.52, and 5.59, respectively). Another two rare variants- p.E4950D and p.A5021V significantly increased MMD risk in Chinese population (dominant model ORs 9.06 and 5.01, respectively). Various other rare variants in RNF213 were identified in Japanese, Chinese, European, and Hispanic American populations without association evidence available yet.
CONCLUSIONS
This meta-analysis shows the critical roles of RNF213 p.R4810K in MMD especially familial MMD and ICASO in Japan, Korea, and China. Except for RNF213 p.R4810K, MMD seems to have more complex determiners in China. Distinct genetic background exists and other environmental or genetic factor(s) may contribute to MMD. Studies focused on delineating the ethnicity-specific factors and pathological role of RNF213 variants in MMD and ICASO are needed.
Topics: Adenosine Triphosphatases; Arterial Occlusive Diseases; Carotid Artery Diseases; Constriction, Pathologic; Genetic Predisposition to Disease; Genetic Variation; Humans; Moyamoya Disease; Ubiquitin-Protein Ligases
PubMed: 29165161
DOI: 10.1186/s12199-017-0680-1 -
Frontiers in Neurology 2022Intracranial angioplasty with a self-expandable stent (SES) is an important endovascular therapy for symptomatic intracranial arterial stenosis. We sought to update the...
BACKGROUND
Intracranial angioplasty with a self-expandable stent (SES) is an important endovascular therapy for symptomatic intracranial arterial stenosis. We sought to update the evaluation of the perioperative safety and long-term outcomes of self-expandable stent for the treatment of symptomatic intracranial arterial stenosis.
METHODS
We comprehensively searched the published literature from each database through Sept 16, 2022, for the PubMed, EMBASE, Web of Science, Cochrane, and Clinical Trials databases. The characteristics of the studies and patients, perioperative complications, and long-term outcomes were extracted. The pooled outcomes and 95% confidence intervals (CIs) were estimated by Stata Statistical Software 14.0.
RESULTS
A total of 4,632 patients from 58 studies were included. The pooled rate of perioperative stroke or death was 6.32% (95% CI 5.04-7.72%); ischemic stroke beyond 30 days through 1 year was 2.72% (95% CI 1.41-4.38%). Perioperative complications differed between the 2014-2022 and 2005-2013 subgroups, as did long-term outcomes between the off-label SES and Wingspan subgroups.
CONCLUSION
The perioperative complications of intracranial angioplasty with SES have been reduced, but the risk of perioperative stroke or death is still higher than that of aggressive medical therapy, and additional studies are needed to determine whether it has better long-term outcomes than aggressive medical therapy. Perioperative complications varied between the 2014-2022 and 2005-2013 subgroups, as did long-term outcomes between the off-label SES and Wingspan subgroups. Given the high level of heterogeneity observed between the included studies, these results should be interpreted with caution and additional studies are needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42022316066.
PubMed: 36698897
DOI: 10.3389/fneur.2022.1074228 -
Genes Jun 2024The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population...
The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation.
Topics: Humans; Adenosine Triphosphatases; Aortic Dissection; Asian People; Genetic Predisposition to Disease; Intracranial Aneurysm; Moyamoya Disease; Polymorphism, Single Nucleotide; Ubiquitin-Protein Ligases
PubMed: 38927660
DOI: 10.3390/genes15060725 -
International Journal of Cardiology Oct 2016The present meta-analysis aimed to compare the diagnostic accuracy of more recent computed tomography coronary angiography (CTCA) with invasive coronary angiography... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The present meta-analysis aimed to compare the diagnostic accuracy of more recent computed tomography coronary angiography (CTCA) with invasive coronary angiography (ICA) in the assessment of graft patency after coronary artery bypass graft surgery (CABG).
MATERIAL AND METHODS
A systematic review was performed using nine electronic databases from their dates of inception to July 2015. Predefined inclusion criteria included studies reporting on comparative outcomes using ≥64 slice multidetector computed tomography (MDCT) and ICA. The primary endpoints included graft occlusion and significant graft stenosis ≥50%. Secondary analyses included the comparison of arterial versus venous graft conduits, and the use of different MDCT techniques.
RESULTS
Thirty-one studies were identified according to selection criteria, involving 1975 patients with 5364 assessed grafts. Combined assessment of stenosis and occlusion for all grafts demonstrated a sensitivity of 96.1% [95% confidence interval (CI) 94.3-97.4%] and specificity of 96.3% (95% CI 95.1-97.3%). CTCA assessment of venous grafts demonstrated higher sensitivity compared to arterial grafts, when testing for both occlusion and stenosis (97.6% vs 89.2%, p=0.004).
CONCLUSION
Results of this study demonstrated that CTCA had a relatively high pooled sensitivity, specificity and negative predictive value compared to ICA. However, patient baseline characteristics varied between studies, and the results should be interpreted with caution. Nonetheless, our results indicate that CTCA should be recognized as an accurate and non-invasive investigation for graft patency in symptomatic patients after CABG.
Topics: Coronary Artery Bypass; Coronary Restenosis; Humans; Multidetector Computed Tomography; Observational Studies as Topic
PubMed: 27439070
DOI: 10.1016/j.ijcard.2016.06.264 -
Surgery Open Science Jun 2023The use of an 'eversion' technique is not unequivocally proven to be superior to carotid endarterectomy with patch angioplasty. An up-to-date systematic review is needed... (Review)
Review
INTRODUCTION
The use of an 'eversion' technique is not unequivocally proven to be superior to carotid endarterectomy with patch angioplasty. An up-to-date systematic review is needed for evaluation of benefits and harms of these two techniques.
METHODS
RCTs comparing eversion technique versus endarterectomy with patch angioplasty in patients with a symptomatic and significant (≥50 %) stenosis of the internal carotid artery were enrolled. Primary outcomes were all-cause mortality rate, health-related quality of life and serious adverse events. Secondary outcomes included 30-day stroke and mortality rate, (a) symptomatic arterial occlusion or restenosis, and adverse events not critical for decision making.
RESULTS
Four RCTs were included with 1272 surgical procedures for carotid stenosis; eversion technique = 643 and carotid endarterectomy with patch closure = 629. Meta-analysis comparing both techniques showed, with a very low certainty of evidence, that eversion technique might decrease the number of patients with serious adverse events (RR 0.47; 95% CI 0.34 to 0.64; ≤ 0.01). However, no difference was found on the other outcomes. TSA demonstrated that the required information sizes were far from being reached for these patient-important outcomes. All patient-relevant outcomes were at low certainty of evidence according to GRADE.
CONCLUSIONS
This systematic review showed no conclusive evidence of any difference between eversion technique and carotid endarterectomy with patch angioplasty in carotid surgery. These conclusions are based on data obtained in trials with very low certainty according to GRADE and should therefore be interpreted cautiously. Until conclusive evidence is obtained, the standard of care according to ESVS guidelines should not be abandoned.
PubMed: 37288439
DOI: 10.1016/j.sopen.2023.05.003 -
Journal of Vascular Research 2022Of the 200 million patients worldwide affected by peripheral arterial disease (PAD), 4% will inevitably require major limb amputation. Previous systematic reviews... (Review)
Review
BACKGROUND
Of the 200 million patients worldwide affected by peripheral arterial disease (PAD), 4% will inevitably require major limb amputation. Previous systematic reviews presented a conflicting body of evidence in terms of vascular endothelial growth factor (VEGF) family member effects upon PAD natural progression. Despite that, modulation of intrinsic angiogenesis mechanisms targeting the VEGF family members still confers an attractive therapeutic target. The aim of the present study was to evaluate current evidence of VEGF modulation in the context of PAD.
METHODS
This is a systematic literature review conducted according to the PRISMA guidelines and registered under PROSPERO database [CRD42021285988]. Independent literature search was performed up to April 1, 2022, on six databases. A total of 22 eligible studies were identified [N: 3, interventional patient studies; N: 19, animal studies]. Animal studies were appraised by the SYRCLE risk of bias tool, while human participant studies were assessed by the Newcastle Ottawa scale. Overall, quality of evidence was deemed fair for both animal and human studies. Main study outcomes were percentage change of injured vessel lumen stenosis and neointimal area formation upon VEGF modulation (inhibition or activation) in comparison with control group.
FINDINGS
Nineteen animal models and three human participant studies were included in the systematic review and assessed separately. Positive modulation of VEGF-A in animal models resulted in a median decrease of 65.58% [95% CI 45.2; 71.87] in lumen stenosis [14 studies]. Furthermore, positive modulation of VEGF-A was found to reduce neointimal area proliferation by a median decrease of 63.41% [95% CI 41.6; 79.59] [14 studies]. Median end of study duration was 28 days [range: 14-84 days]. Data were insufficient to assess these outcomes with respect to VEGF-B or VEGF-C modulation. The limited number of available human studies presented inadequate outcome assessment despite their overall fair NOS grading.
INTERPRETATION
VEGF-A-positive modulation decreases lumen stenosis and neointimal hyperplasia in PAD simulation animal models. Previously identified variability among outcomes was found to strongly stem from the variability of experimental designs. Clinical applicability and safety profile of VEGF-A in the context of PAD remain to be defined by a robust and uniformly designed body of further animal model-based experiments.
Topics: Animals; Humans; Vascular Endothelial Growth Factor A; Constriction, Pathologic; Peripheral Arterial Disease
PubMed: 36380643
DOI: 10.1159/000527079 -
Stroke Jul 2023Effectiveness of carotid procedures (surgery and stenting) in patients with asymptomatic carotid artery stenosis (ACAS) depends on the absolute risk reduction that...
BACKGROUND
Effectiveness of carotid procedures (surgery and stenting) in patients with asymptomatic carotid artery stenosis (ACAS) depends on the absolute risk reduction that patients might receive from these procedures. We aimed to quantify the risk of ipsilateral ischemic stroke and examined temporal trends and determinants of these risks in patients with ACAS treated conservatively.
METHODS
We conducted a systematic review from inception to March 9, 2023, of peer-reviewed trials and cohort studies describing ipsilateral ischemic stroke risk in medically treated patients with ACAS of ≥50%. Risk of bias was assessed with an adapted version of the Quality in Prognosis Studies tool. We calculated the annual incidence rates of ipsilateral ischemic stroke. We explored temporal trends and associations of sex and degree of stenosis with ipsilateral ischemic stroke using Poisson metaregression analysis and incidence rate ratios, respectively.
RESULTS
After screening 5915 reports, 73 studies describing ipsilateral ischemic stroke rates of 28 625 patients with midyear of recruitment ranging from 1976 to 2014 were included. The incidence of ipsilateral ischemic stroke was 0.98 (95% CI, 0.93-1.04) per 100 patient-years (median duration of follow-up, 3.3 years). The incidence decreased 24% with every 5 years more recent midyear of recruitment (rate ratio, 0.76 [95% CI, 0.73-0.78]). Incidence rates of ipsilateral ischemic stroke were lower in female patients (rate ratio, 0.74 [95% CI, 0.63-0.87]) and in patients with moderate versus severe stenosis when assessed in cohort studies, with incidence rate ratios of 0.41 ([95% CI, 0.35-0.49] cutoff, 70%) and 0.42 ([95% CI, 0.30-0.59] cutoff, 80%).
CONCLUSIONS
Reported risks of ipsilateral ischemic stroke in patients with ACAS have declined 24% every 5 years from mid-1970s onward, further challenging the routine use of carotid procedures. Risks were lower in female patients and more than twice as high with severe compared with moderate ACAS. Inclusion of these findings in individualized risk assessment can help to determine the benefit of carotid procedures in selected individual patients with ACAS.
REGISTRATION
URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021222940.
Topics: Humans; Female; Carotid Stenosis; Stroke; Constriction, Pathologic; Cohort Studies; Ischemic Stroke; Endarterectomy, Carotid; Risk Factors
PubMed: 37309688
DOI: 10.1161/STROKEAHA.122.041921 -
Cerebrovascular Diseases (Basel,... 2015Ultrasound is the most commonly used imaging modality for assessing carotid artery stenosis. A number of studies have demonstrated that surface irregularities,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ultrasound is the most commonly used imaging modality for assessing carotid artery stenosis. A number of studies have demonstrated that surface irregularities, heterogeneous echotexture and hypoechoic plaques are risk factors for acute ischemic stroke. We performed a systematic review and meta-analysis of the literature to better define the risk of stroke based on the sonographic characteristics of carotid plaques.
MATERIALS AND METHODS
We performed a comprehensive search for studies reporting imaging findings of symptomatic and asymptomatic carotid plaques on ultrasound using MEDLINE and EMBASE. We included both case-control and cohort studies examining the relationship between complex plaque and acute ischemic stroke or transient ischemic attack. Complex plaque was defined as plaque that had any of the following characteristics: heterogeneous echogenicity, echolucency, neovascularization, surface irregularity, ulceration, and intraplaque motion. Meta-analyses using the random-effects model were performed for complex plaque and each of the individual complex plaque characteristics. p < 0.05 was considered statistically significant. We explored the impact of publication bias by constructing funnel plots and testing their symmetry. We conducted the meta-analysis using Comprehensive Meta-analysis version 2.2, Englewood, N.J., USA.
RESULTS
A total of 1,013 articles were screened and 23 studies with 6,706 carotid plaques were included. Ultrasound plaque characteristics with a higher prevalence in individuals with symptomatic compared to asymptomatic carotid artery stenosis included plaque neovascularity (OR = 19.68, 95% CI = 3.14-123.16), complex plaque (OR = 5.12, 95% CI = 3.42-7.67), plaque ulceration (OR = 3.58, 95% CI = 1.66-7.71), plaque echolucency (OR = 3.99, 95% CI = 3.06-5.19) and intraplaque motion (OR = 1.57, 95% CI = 1.02-2.41). Variables not associated with symptom status included heterogenous echotexture (OR = 2.68, 95% CI = 0.56-12.80) and surface irregularity without ulceration (OR = 2.38, 95% CI = 0.70-8.11). No evidence of publication bias was observed based on Eggers test (p value of 0.05 for complex plaque and 0.53 for plaque echolucency). The remaining plaque features had insufficient data to assess for publication bias.
CONCLUSIONS
Our meta-analysis and systematic review of the literature demonstrated that plaques with complex features, particularly those with echolucency, neovascularization, ulceration and intraplaque motion are associated with ischemic symptoms. Assessment of carotid plaque on ultrasound may provide stroke risk information beyond measurement of luminal stenosis. Thus, sonographic evaluation of carotid artery stenosis should focus on the detection of these plaque characteristics in addition to quantifying the degree of stenosis.
Topics: Carotid Arteries; Carotid Stenosis; Humans; Ischemic Attack, Transient; Plaque, Atherosclerotic; Risk Factors; Stroke; Ultrasonography
PubMed: 26279159
DOI: 10.1159/000437339 -
European Journal of Vascular and... Mar 2022The aim was to enhance understanding of the role of platelet biomarkers in the pathogenesis of vascular events and risk stratifying patients with asymptomatic or... (Review)
Review
OBJECTIVE
The aim was to enhance understanding of the role of platelet biomarkers in the pathogenesis of vascular events and risk stratifying patients with asymptomatic or symptomatic atherosclerotic carotid stenosis.
DATA SOURCES
Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
REVIEW METHODS
A systematic review collated data from 1975 to 2020 on ex vivo platelet activation and platelet function/reactivity in patients with atherosclerotic carotid stenosis.
RESULTS
Forty-three studies met the inclusion criteria; the majority included patients on antiplatelet therapy. Five studies showed increased platelet biomarkers in patients with ≥ 30% asymptomatic carotid stenosis (ACS) vs. controls, with one neutral study. Preliminary data from one study suggested that quantification of "coated platelets" in combination with stenosis severity may aid risk stratification in patients with ≥ 50% - 99% ACS. Platelets were excessively activated in patients with ≥ 30% symptomatic carotid stenosis (SCS) vs. controls (≥ 11 positive studies and one neutral study). Antiplatelet-High on Treatment Platelet Reactivity (HTPR), previously called "antiplatelet resistance", was observed in 23% - 57% of patients on aspirin, with clopidogrel-HTPR in 25% - 100% of patients with ≥ 50% - 99% ACS. Aspirin-HTPR was noted in 9.5% - 64% and clopidogrel-HTPR in 0 - 83% of patients with ≥ 50% SCS. However, the data do not currently support the use of ex vivo platelet function/reactivity testing to tailor antiplatelet therapy outside of a research setting. Platelets are excessively activated (n = 5), with increased platelet counts (n = 3) in recently symptomatic vs. asymptomatic patients, including those without micro-emboli on transcranial Doppler (TCD) monitoring (n = 2). Most available studies (n = 7) showed that platelets become more reactive or activated following carotid endarterectomy or stenting, either as an acute phase response to intervention or peri-procedural treatment.
CONCLUSION
Platelets are excessively activated in patients with carotid stenosis vs. controls, in recently symptomatic vs. asymptomatic patients, and may become activated/hyper-reactive following carotid interventions despite commonly prescribed antiplatelet regimens. Further prospective multicentre studies are required to determine whether models combining clinical, neurovascular imaging, and platelet biomarker data can facilitate optimised antiplatelet therapy in individual patients with carotid stenosis.
Topics: Aspirin; Biomarkers; Blood Platelets; Carotid Stenosis; Humans; Platelet Aggregation Inhibitors; Stroke
PubMed: 35181225
DOI: 10.1016/j.ejvs.2021.10.045 -
Journal of Cardiothoracic Surgery Jul 2023Valve-sparing aortic root replacement (VSARR) is a safe and effective surgical procedure to treat aortic root aneurysm. This meta-analysis aimed to investigate how this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Valve-sparing aortic root replacement (VSARR) is a safe and effective surgical procedure to treat aortic root aneurysm. This meta-analysis aimed to investigate how this procedure might differ in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).
DESIGN
Meta-analysis with meta-regression and systematic review.
SETTING
Systematic search in the following databases: PubMed, Cochrane Central Register of Controlled Trials, and Embase.
INTERVENTIONS
All observational studies of VSARR in patients with BAV or TAV were included in our study. Studies were included without any restrictions on language or publication date. A trial sequential analysis and a post-hoc meta-regression was performed on the main outcomes.
RESULT
Eleven articles met the inclusion criteria. A total of 1138 patients in BAV group, and 2125 patients in TAV group. No significant differences in gender and age were observed between BAV and TAV patients. BAV and TAV patients showed no differences in in-hospital mortality rate [0.00% vs. 1.93%; RR (95% CI) 0.33 (0.09, 1.26), I = 0%, P = 0.11] and the rate of in-hospital reoperation [5.64% vs. 5.99%; RR (95% CI) 1.01(0.59, 1.73), I = 33%, P = 0.98]. The overall long-term mortality rate of BAV patients was better than that of TAV patients [1.63% vs. 8.15%; RR (95% CI) 0.34 (0.13, 0.86), I = 0%, P = 0.02]. During the follow-up observation period, patients in TAV group showed small but no statistic advantage in 3-year, 5-year, and over 10-year incidences of reintervention. Regarding the secondary endpoints, the two groups showed similar aortic cross-clamping time and total cardiopulmonary bypass time.
CONCLUSION
The VSARR techniques yielded similar clinical outcomes in both BAV and TAV patients. Although patients with BAV might have a higher incidence of reinterventions after initial VSARR, it is still a safe and effective approach to treat aortic root dilation with or without aortic valve insufficiency. TAV patients showed small but no statistic advantage in long-term (over 10 years) reintervention rate, which means, patients with BAV may face a higher risk of reintervention in the clinic.
Topics: Humans; Aortic Valve; Bicuspid Aortic Valve Disease; Heart Valve Diseases; Aorta; Tricuspid Valve; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis; Retrospective Studies; Treatment Outcome; Observational Studies as Topic
PubMed: 37400892
DOI: 10.1186/s13019-023-02329-8