scholarly journals Clinical and Imaging Predictors of Recurrent Ischemic Stroke: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 45 (5-6) ◽  
pp. 279-287 ◽  
Author(s):  
Frans Kauw ◽  
Richard A.P. Takx ◽  
Hugo W.A.M. de Jong ◽  
Birgitta K. Velthuis ◽  
L. Jaap Kappelle ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Lower Risk ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Large Artery ◽  
Cortical Lesions ◽  
Level Of Evidence ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
History Of

Background: Predictors of recurrent ischemic stroke are less well known in patients with a recent ischemic stroke than in patients with transient ischemic attack (TIA). We identified clinical and radiological factors for predicting recurrent ischemic stroke in patients with recent ischemic stroke. Methods: A systematic search in PubMed, Embase, Cochrane Library, and CINAHL was performed with the terms “ischemic stroke,” “predictors/determinants,” and “recurrence.” Quality assessment of the articles was performed and the level of evidence was graded for the articles included for the meta-analysis. Pooled risk ratios (RR) and heterogeneity (I2) were calculated using inverse variance random effects models. Results: Ten articles with high-quality results were identified for meta-analysis. Past medical history of stroke or TIA was a predictor of recurrent ischemic stroke (pooled RR 2.5, 95% CI 2.1–3.1). Small vessel strokes were associated with a lower risk of recurrence than large vessel strokes (pooled RR 0.3, 95% CI 0.1–0.7). Patients with stroke of an undetermined cause had a lower risk of recurrence than patients with large artery atherosclerosis (pooled RR 0.5, 95% CI 0.2–1.1). We found no studies using CT or ultrasound for the prediction of recurrent ischemic stroke. The following MRI findings were predictors of recurrent ischemic stroke: multiple lesions (pooled RR 1.7, 95% CI 1.5–2.0), multiple stage lesions (pooled RR 4.1, 95% CI 3.1–5.5), multiple territory lesions (pooled RR 2.9, 95% CI 2.0–4.2), chronic infarcts (pooled RR 1.5, 95% CI 1.2–1.9), and isolated cortical lesions (pooled RR 2.2, 95% CI 1.5–3.2). Conclusions: In patients with a recent ischemic stroke, a history of stroke or TIA and the subtype large artery atherosclerosis are associated with an increased risk of recurrent ischemic stroke. Predictors evaluated with MRI include multiple ischemic changes and isolated cortical lesions. Predictors of recurrent ischemic stroke concerning CT or ultrasound have not been published.

scholarly journals Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xi Chen ◽  
Hairui Li ◽  
Shibai Zhu ◽  
Yiou Wang ◽  
Wenwei Qian
Keyword(s):  
Local Recurrence ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Meta Analysis ◽  
Cell Tumor ◽  
Cochrane Library ◽  
Control Group ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
The Cochrane Library

Abstract Background: In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery. Methods: Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted. Result: Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P<0.02) and inferior 5 year recurrence free survival(P=0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P=0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P=0.24). Conclusion: Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.

scholarly journals Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xi Chen ◽  
Hairui Li ◽  
Shibai Zhu ◽  
Yiou Wang ◽  
Wenwei Qian
Keyword(s):  
Local Recurrence ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Meta Analysis ◽  
Cell Tumor ◽  
Cochrane Library ◽  
Control Group ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
The Cochrane Library

Abstract Background In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery. Methods Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted. Result Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P<0.02) and inferior 5 year recurrence free survival(P=0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P=0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P=0.24). Conclusion Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.

scholarly journals Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xi Chen ◽  
Hairui Li ◽  
Shibai Zhu ◽  
Yiou Wang ◽  
Wenwei Qian
Keyword(s):  
Local Recurrence ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Meta Analysis ◽  
Cell Tumor ◽  
Cochrane Library ◽  
Control Group ◽  
Risk Of Recurrence ◽  
Increased Risk ◽  
The Cochrane Library

Abstract Background In 2013, denosumab was introduced as peri-operative adjuvant treatment for giant cell tumor (GCT) of bone as it inhibits osteoclast activity. It is suggested that denosumab relives pain, facilitate curettage in lesions requiring resection initially. However, controversy remains whether denosumab increases the risk of local recurrence after surgery. Methods Medline, Embase and the Cochrane Library were comprehensively searched in June 2019 to identify studies investigating the clinical outcome of GCT of bone with and without peri-operative denosumab after surgery. Data were gathered and a meta-analysis was conducted. Result Ten studies with 1082 cases (169 in denosumab group, 913 in control group) were included. Overall, denosumab was associated with significantly higher risk of recurrence(P<0.02) and inferior 5 year recurrence free survival(P=0.000). Denosumab and curettage has a relatively higher risk of recurrence comparing to curettage alone(P=0.07). The risk of recurrence is not significantly increased if denosumab was administered both preoperatively and postoperatively(P=0.24). Conclusion Administration of denosumab is associated with increased risk of recurrence due to a variety of reasons, though it is proven effective in relieving pain, enabling curettage and improved functional outcome. Post-operative denosumab is recommended as it continuously suppress/eliminate residue tumor cells.

Factors Associated With an Increased Risk of Recurrence After a First-Time Patellar Dislocation: A Systematic Review and Meta-analysis

2019 ◽  
Vol 48 (10) ◽  
pp. 2552-2562 ◽  
Author(s):  
Lachlan S. Huntington ◽  
Kate E. Webster ◽  
Brian M. Devitt ◽  
John P. Scanlon ◽  
Julian A. Feller
Keyword(s):  
Risk Factors ◽  
Patellar Dislocation ◽  
Trochlear Dysplasia ◽  
Meta Analysis ◽  
Risk Of Recurrence ◽  
Multiple Risk Factors ◽  
Increased Risk ◽  
Lateral Patellar Dislocation ◽  
History Of ◽  
First Time

Background: Recurrent dislocations after a first-time lateral patellar dislocation may occur in more than 50% of patients and can cause long-term disability. Many factors have been suggested to influence the risk of recurrence. Purpose: To systematically review and quantitatively synthesize the literature for factors associated with an increased risk of recurrence after a first-time patellar dislocation. Study Design: Systematic review and meta-analysis of observational studies. Methods: A total of 4 electronic databases were searched to identify relevant studies published before February 7, 2019. A quality assessment was performed with the National Heart, Lung, and Bone Institute quality assessment score. Factors assessed for their effect on the recurrence rate were documented, and the rates of recurrence were compared. Pooled dichotomous data were analyzed using random-effects meta-analysis with odds ratios (ORs). Results: A total of 17 studies met the criteria for inclusion. The overall rate of recurrent dislocations after a first-time lateral patellar dislocation was 33.6%. An increased risk of recurrence was reported in patients with a younger age (OR, 2.61; P < .00001), open physes (OR, 2.72; P < .00001), trochlear dysplasia (OR, 4.15; P = .009), an elevated tibial tuberosity–trochlear groove (TT-TG) distance (OR, 2.87; P < .00001), and patella alta (OR, 2.38; P = .004). Sex, patterns of medial patellofemoral ligament injury, and history of contralateral dislocations were not found to be associated with an increased recurrence rate ( P≥ .05). In studies that reported on the presence of multiple risk factors, recurrence rates were 7.7% to 13.8% when no risk factors were present but increased to 29.6% to 60.2% when 2 risk factors were present and to 70.4% to 78.5% when 3 risk factors were present. Conclusion: Younger age, open physes, trochlear dysplasia, elevated TT-TG distance, and patella alta were key risk factors for the recurrence of lateral patellar dislocations. Despite being not infrequently cited as risk factors, patient sex and a history of contralateral dislocations were not found to be significant risk factors. The presence of multiple risk factors increased the risk, and the development of predictive instability scores in large patient cohorts using all established risk factors should be a focus of future studies.

scholarly journals A meta-analysis of adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Chen Xiuju ◽  
Wang Zhen ◽  
Shi Yanchao
Keyword(s):  
Ischemic Stroke ◽  
Stroke Risk ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Adiponectin Gene ◽  
China National Knowledge Infrastructure ◽  
Single Nucleotide ◽  
Knowledge Infrastructure ◽  
Increased Risk ◽  
Ischemic Stroke Risk

AbstractSeveral studies have investigated the correlation between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk. However, the results were not conclusive with each other. Therefore, to overcome this obstacle, we performed this meta-analysis to further explicate the adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility. Case-control or cohort studies focused on adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk were electronic searched in the databases of Medline, Pubmed, Cochrane library, Excerpta Medica database(EMBASE) and China National Knowledge Infrastructure (CNKI). All the potentially relevant studies were included in this meta-analysis. The association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke was expressed by odds ratio with its confidence interval. Publication bias has been assessed by begg’s funnel plot. All the analyses have been performed by Revman 5.1 statistical software. Finally, a total of six studies with 1,345 cases and 1,421 controls were included in this meta-analysis. Our results demonstrated that there was a significant association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk (p<0.05). People with G single nucleotide of adiponectin gene have the increased risk of developing ischemic stroke compared to T single nucleotide.

scholarly journals Risk for ischemic stroke and coronary heart disease associated with migraine and migraine medication among older adults

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Emily C. McKinley ◽  
Christine L. Lay ◽  
Robert S. Rosenson ◽  
Ligong Chen ◽  
Victoria Chia ◽  
...  
Keyword(s):  
Older Adults ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ischemic Stroke ◽  
Lower Risk ◽  
Coronary Revascularization ◽  
Opioid Medication ◽  
Increased Risk ◽  
History Of ◽  
Migraine Medication

Abstract Background Migraine has been associated with cardiovascular disease (CVD) events among middle-aged adults. The objective of this study was to determine the risk for ischemic stroke and coronary heart disease (CHD) events among older adults with versus without migraine. Methods This retrospective cohort study was conducted using data from US adults ≥66 years of age with Medicare health insurance between 2008 and 2017. After stratification by history of CVD, patients with a history of migraine were matched 1:4 to those without a history of migraine, based on calendar year, age, and sex. Patients were followed through December 31, 2017 for ischemic stroke and CHD events including myocardial infarction or coronary revascularization. All analyses were done separately for patients with and without a history of CVD. Results Among patients without a history of CVD (n = 109,950 including n = 21,990 with migraine and n = 87,960 without migraine), 1789 had an ischemic stroke and 3552 had a CHD event. The adjusted hazard ratio (HR) among patients with versus without migraine was 1.20 (95% confidence interval [95%CI], 1.07–1.35) for ischemic stroke and 1.02 (95%CI, 0.93–1.11) for CHD events. Compared to patients without migraine, those with migraine who were taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.43 [95%CI, 1.20–1.69]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.79 [95%CI, 0.67–0.93]). Among patients with a history of CVD (n = 79,515 including n = 15,903 with migraine and n = 63,612 without migraine), 2960 had an ischemic stroke and 7981 had a CHD event. The adjusted HRs (95%CI) for ischemic stroke and CHD events associated with migraine were 1.27 (1.17–1.39) and 0.99 (0.93–1.05), respectively. Patients with migraine taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.21 [95%CI, 1.07–1.36]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.83 [95%CI, 0.72–0.95]), each versus those without migraine. Conclusions Older adults with migraine are at increased risk for ischemic stroke. The risk for ischemic stroke among older adults with migraine may differ by migraine medication classes.

scholarly journals Migraine and the risk of stroke: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Mei-Jun Shu ◽  
Meng-Yao Wan ◽  
Ding-Ding Zhang ◽  
Hang Shen ◽  
Yi-Cheng Zhu
Keyword(s):  
Ischemic Stroke ◽  
Cohort Studies ◽  
Migraine With Aura ◽  
Hemorrhagic Stroke ◽  
Data Extraction ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Increased Risk ◽  
Data Extraction Form ◽  
The Cochrane Library

Abstract Background and Purpose The relationship between migraine status and stroke risk was not determined. This study aims to summarize the existing evidence from prospective cohort studies. Methods We searched Pubmed, Embase, and the Cochrane Library from inception to Dec 2020, and all retrieved articles were screened by two independent reviewers. We extracted and assessed data by a structured and standardized data extraction form. The effect values were calculated using a random-effects model. This review was prospectively registered with the PROSPERO database (CRD42020197137). Results Out of 10,705 records, 19 cohort studies including a combined total of 3,523,235 participants were finally included in the meta-analysis. At a mean of 9.31 years (range 1.4–20 years) follow-up, migraine was associated with an elevated risk of total stroke (pooled RR 1.69, 95%CI 1.36 to 2.11, P < 0.001, I2 = 86%), ischemic stroke (pooled RR 1.46, 95%CI 1.14 to 1.87, P < 0.001, I2 = 95.8%), and hemorrhagic stroke (pooled RR 1.37, 95%CI 1.04 to 1.81, P < 0.001, I2 = 85.9%). The prespecified subgroup analysis found that this kind of relationship existed in migraine with aura (ischemic stroke: pooled RR 1.75, 95%CI 1.35 to 2.29, P < 0.001, I2 = 81.7%; hemorrhagic stroke: pooled RR 1.63, 95%CI 1.26 to 2.10, P = 0.266, I2 = 23.2%), but not migraine without aura. Conclusions Our study implies that migraine, particularly migraine with aura, was associated with an increased risk for both ischemic and hemorrhagic stroke.

scholarly journals The association of MTHFR C677T variant with increased risk of ischemic stroke in the elderly population: a meta-analysis of observational studies

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Guilin Chang ◽  
Zheng Kuai ◽  
Jia Wang ◽  
Jiayu Wu ◽  
Kan Xu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Elderly Population ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
The Elderly ◽  
Cochrane Library ◽  
Case Control Studies ◽  
Eligibility Criteria ◽  
Increased Risk

Abstract Background C677T point mutation in methylenetetrahydrofolate reductase (MTHFR) gene have been found to be associated with ischemic stroke in general population, while the results seem inconsistent. We aim to assess the association between variant MTHFR C677T variant and increased risk of ischemic stroke and focus on the elderly population. Methods We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies. Odds ratios (ORs) were calculated with the two-tailed 95% confidence intervals (CIs) by using a random effects model to evaluate any possible association. Among the Chinese and non-Chinese populations, we conducted a subgroup analysis. Results The electronic database search yielded 1,358 citations as of December 2017; finally, nine case-control studies involving 3,337 subjects fulfilled our eligibility criteria for inclusion in the study. The pooled results showed that MTHFR C677T variant increased the risk of ischemic stroke (OR = 1.23, 95%CI 1.06–1.43, P = 0.0067 for CT + TT vs. CC; OR = 1.18, 95%CI 1.01–1.38, P = 0.0333 for CT vs. CC; OR = 1.41, 95%CI 1.14–1.75, P = 0.0016 for TT vs. CC; OR = 1.27, 95%CI 1.05–1.54, P = 0.0145 for TT vs. CC + CT; OR = 1.18, 95%CI 1.06–1.31, P = 0.0023 for T-allele vs. C-allele). Further subgroup analyses in the Chinese population indicated that MTHFR C677T variant was associated with a higher risk of ischemic stroke. Conclusion Our findings showed that T-allele increases risk for stroke in the pooled sample. This association was statistically significant in the Chinese cohorts and showed a similar trend in the non-Chinese cohorts. (Word count: 237).

Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes

Stroke ◽  
2021 ◽  
Author(s):  
Jie Xu ◽  
Aichun Cheng ◽  
Bo Song ◽  
Mingming Zhao ◽  
Jing Xue ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cox Regression ◽  
Meta Analysis ◽  
Artery Occlusion ◽  
Hazard Ratio ◽  
Stroke Recurrence ◽  
Large Artery ◽  
Small Artery ◽  
Increased Risk ◽  
Small Artery Occlusion

Background and Purpose: Trimethylamine N-oxide (TMAO) has been recognized as a risk factor for cardiovascular disease. However, the role of TMAO in ischemic stroke remains unclear. As we know, ischemic stroke is a heterogeneous disease with variable pathogenesis. Hence, we aimed to investigate the association between TMAO and stroke recurrence according to etiology subtypes. Methods: A total of 10 756 ischemic stroke/transient ischemic attack patients from the Third China National Stroke Registry were enrolled, and 1-year follow-up data for stroke recurrence were analyzed. TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria was used to classify the etiology subtypes. Plasma TMAO levels were quantified by liquid chromatography–mass spectrometry. The association between TMAO and stroke outcomes was analyzed using Cox regression models. We also conducted a meta-analysis on the association of TMAO levels and stroke risk. Results: Elevated TMAO level was independently associated with the risk of stroke recurrence (Q4 versus Q1: adjusted hazard ratio, 1.37 [95% CI, 1.15–1.64]) in multivariate Cox regression model. After stratification by TOAST subtypes, there was a significant association between TMAO and stroke recurrence in small artery occlusion subtype (adjusted hazard ratio, 1.43 [95% CI, 1.03–2.00]) but not in the others subtype (large-artery atherosclerosis, 1.19 [0.95–1.48]; cardioembolism, 1.54 [0.95–2.48]; others, 1.19 [0.98–1.44]). The meta-analysis reported on stroke recurrence for the highest versus lowest TMAO levels with a pooled hazard ratio of 1.66 (95% CI, 0.91–3.01) and similarly found an increased risk of stroke recurrence. Conclusions: Elevated TMAO level is associated with increased risk of stroke recurrence in patients with small artery occlusion subtype, but this association seems to be attenuated in large-artery atherosclerosis, cardioembolism, and others subtypes.

Risk of adverse cardiovascular events (CVE) and incident diabetes mellitus (DM) in patients (pts) with prostate cancer (PC) treated with androgen deprivation therapy (ADT): A meta-analysis of adjusted observational results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15192-e15192
Author(s):  
Lorenzo D'Ambrosio ◽  
Federica Brusa ◽  
Fabrizio D'Ascenzo ◽  
Erica Cavallero ◽  
Giuseppe Biondi-Zoccai ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Cardiovascular Death ◽  
Cochrane Library ◽  
Adjusted Risk ◽  
Inverse Variance ◽  
Increased Risk ◽  
History Of ◽  
Secondary Endpoints ◽  
Meta Regression Analysis ◽  
Ischemic Attack

e15192 Background: ADT is a mainstay treatment in pts with PC and is supposedly associated to an unfavorable metabolic and cardiovascular profile. Recently, a meta-analysis of randomized controlled trials (RCT) found no association between ADT and increased risk of CVE (JAMA 2011). However, no conclusive data were available about ADT association with metabolic changes and adverse CVE or DM because of pts selection in RCT. Therefore, we performed a meta-analysis of adjusted observational results in order to look for DM and CVE onset in an ADT unselected population. Methods: Medline, Cochrane Library and Biomed Central were searched for articles addressing adverse events related to ADT in patients with PC. Selection criteria were: not RCT, pts assigned to ADT or not, adjusted risk of CVE and DM according to ADT. Exclusion criteria were: duplicate publication, comparison of two different strategies of ADT (different drugs or duration). Cardiovascular death was the primary endpoint; non-fatal myocardial infarction (MI), stroke/transient ischemic attack (TIA) and new DM onset were secondary endpoints. Random effects model with generic inverse variance weighting was used to estimate adjusted risks as odds ratios (OR) with 99% confidence interval (CI). Results: We selected 12/2100 screened studies. We included 208643 pts of which 102177 received ADT. At a follow up of 5 years (4-7.5), ADT did not result as an independent risk factor for cardiovascular death (OR= 1.04; 99% CI= 0.94-1.14). No increased risk of MI (OR= 1.13; CI= 0.86-1.48) or of stroke/TIA (OR= 1.11; CI= 0.78-1.57) were detected. Incident DM was more frequent among ADT pts (OR= 1.32; CI= 1.14-1-53). Even in 7205 pts with previous CVE (2450 received ADT), ADT was not associated with an increased risk of overall death (OR= 1.23; CI= 0.87-1.75). Meta-regression analysis showed no significant interactions between duration of ADT and cardiovascular death or incident DM. Conclusions: In non-selected pts,ADT appears to increase the risk of incident DM, but not of CVE or stroke/TIA. Moreover, overall mortality is not increased in pts with a history of CVE.

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