Benefits of First Pass Recanalization in Basilar Strokes Based on Initial Clinical Severity.

PURPOSE: Randomized trials demonstrating the benefits of thrombectomy for basilar artery occlusions have enrolled an insufficient number of patients with a National Institutes for Health Stroke Scale (NIHSS) score < 10 and shown discrepant results for patients with an NIHSS > 20. Achieving a first pass recanalization (FPR) improves clinical outcomes in stroke. We aimed to evaluate the effect of the FPR on outcomes among basilar artery occlusion patients, characterized by prethrombectomy initial NIHSS score. METHODS: We retrospectively analyzed the Endovascular Treatment in Ischemic Stroke (ETIS) registry of 279 basilar artery occlusion patients treated with thrombectomy from 6 participating centers. We compared the 90-day clinical outcomes of achieving a FPR versus no FPR, categorized by initial clinical severity: mild (NIHSS < 10), moderate (NIHSS 10-20) and severe (NIHSS > 20). We used Poisson regression with robust error variance to determine the effect of the NIHSS score on the association between FPR and outcomes. RESULTS: The FPR patients with NIHSS < 10 or NIHSS 10-20 were more likely to have a favorable clinical outcome (modified Rankin scale, mRS 0-3) than non-FPR patients (relative risk, RR = 1.32, 95% confidence interval, CI: 1.04, 1.66, p-value = 0.0213, and RR = 1.79, 95% CI: 1.26, 2.53, p-value = 0.0011, respectively). A similar benefit was not found in patients with severe symptoms. We found a significantly lower risk of poor clinical outcome (mRS 4-6) in FPR patients with NIHSS 10-20, but not among patients with an NIHSS > 20. CONCLUSION: Achieving a FPR in basilar artery occlusion patients with mild (NIHSS < 10) or moderate (NIHSS 10-20) symptoms is associated with better clinical outcomes, but not in patients with severe symptoms. These results support the importance of further clinical trials on the benefits of thrombectomy in severe strokes.

Inherited thrombophilia gene mutations and risk of venous thromboembolism in patients with cancer: A systematic review and meta-analysis.

In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia. In September 2022, we searched Medline, EMBASE, and Cochrane Central. Two reviewers screened the abstracts/full texts and assessed study quality using the Quality in Prognostic Studies tool. We used Mantel-Haenszel random-effects models to estimate pooled odds ratios (OR) of VTE and 95% confidence intervals (95%CI). We included 37 and 28 studies in the systematic review and meta-analysis, respectively. Most studies focused on specific cancer types and hematologic malignancies were rare. The risk of VTE was significantly higher in cancer patients with non-O (compared with O) blood types (OR: 1.56 [95% CI: 1.28-1.90]), Factor V Leiden, and Prothrombin Factor II G20210A mutations compared with wild types (OR: 2.28 [95% CI: 1.51-3.48] and 2.14 [95% CI: 1.14-4.03], respectively). Additionally, heterozygous and homozygous methylenetetrahydrofolate reductase C677T had ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively. Among those with Plasminogen-Activator Inhibitor-1 4G/5G, Vascular Endothelial Growth Factor (VEGF) A C634G, and VEGF C2578A mutations, there was no significant association with VTE. In conclusion, this meta-analysis provided evidence that non-O blood types, Factor V Leiden, and Prothrombin Factor II G20210A mutations are important genetic risk factors for VTE in cancer patients.

Dual Antiplatelet Therapy in Minor Stroke/Transient Ischemic Attack - An Updated Network Meta-Analysis.

We previously analyzed five trials on ticagrelor/aspirin versus clopidogrel/aspirin in patients with minor stroke/ TIA in a network meta-analysis. We updated our search and identified 311 new citations with one study for inclusion: CHANCE2 enrolled patients with CYP2C19 loss-of-function alleles and randomized them to ticagrelor/aspirin or clopidogrel/aspirin. Pooling of CHANCE2 with the original studies could not be completed due to violation of NMA assumptions, due to significant inconsistency. This suggests patients with CYP2C19 loss-of-function alleles represent a subpopulation that is inherently different from the general stroke population in their antiplatelet response. Results from CHANCE-2 may not be generalizable without genotype testing.

Thrombophilia gene mutations predict venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

BACKGROUND: Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear. OBJECTIVES: Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy. METHODS: We conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated. RESULTS: Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding. CONCLUSION: Our results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.

Effect modification of age and hypertension on cancer and prevalence of self-reported stroke - A cross-sectional study.

The objective of this study was to examine the effect modification of age on the relationship between cancer and prevalence of self-reported stroke. We used cross-sectional data from the 2015-2016 iteration of the Canadian Community Health Survey. A multivariable logistic regression model was used to assess the association between cancer and self-reported stroke. Covariates were assessed for effect modification using the maximum likelihood estimation method. We analyzed 86,809 subjects; the prevalence of self-reported stroke was 1.11%. The odds ratio for the association between cancer and self-reported stroke was 1.26 (95% CI 0.98-1.61) after adjusting for age, sex, dyslipidemia, hypertension, diabetes, heart disease, education, and household income. Age and hypertension were found to be effect modifiers, and the association between cancer and self-reported stroke was stronger in younger adults and in those without hypertension. These results suggest that cancer-associated strokes may have unique underlying mechanisms compared to conventional strokes.

Incidence of stroke in the first year after diagnosis of cancer-A systematic review and meta-analysis.

Background: Patients newly diagnosed with cancer represent a population at highest risk for stroke. The objective of this systematic review and meta-analysis was to estimate the incidence of stroke in the first year following a new diagnosis of cancer. Methods: We searched MEDLINE and EMBASE from January 1980 to June 2021 for observational studies that enrolled adults with a new diagnosis of all cancers excluding non-melanoma skin cancer, and that reported the incidence of stroke at 1 year. PRISMA guidelines for meta-analyses were followed. Two reviewers independently extracted data and appraised risk of bias. We used the Dersimonian and Laird random effects method to pool cumulative incidences after logit transformation, and reported pooled proportions as percentages. Statistical heterogeneity was assessed using the I 2 statistic. Results: A total of 12,083 studies were screened; 41 studies were included for analysis. Data from 2,552,121 subjects with cancer were analyzed. The cumulative incidence of total stroke at 1 year was 1.4% (95% CI 0.9-2.2%), while the pooled incidence of ischemic stroke was 1.3% (95% CI 1.0-1.8%) and 0.3% (95% CI 0.1-0.9%) for spontaneous intracerebral hemorrhage (ICH), with consistently high statistical heterogeneity (>99% I 2). Conclusion: The estimated incidence of stroke during the first year after a new diagnosis of cancer is 1.4%, with a higher risk for ischemic stroke than ICH. Cancer patients should be educated on the risk of stroke at the time of diagnosis. Future studies should evaluate optimal primary prevention strategies in this high-risk group of patients. Systematic review registration: https://osf.io/ucwy9/.

Growth Differentiation Factor-15, High-Sensitivity Cardiac Troponin T, and N-Terminal pro-B-type Natriuretic Peptide for Predicting Risk of Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy.

Growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (hs-TnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased risk of venous thromboembolism (VTE) in noncancer patients. However, the performance of these biomarkers in cancer patients is unknown. Our objective was to assess performance of these biomarkers in predicting VTE in cancer patients at intermediate to high risk for VTE (Khorana Score ≥ 2). We used 1-month plasma samples from AVERT trial patients to determine if GDF-15, NT-proBNP, and hs-TnT levels are associated with VTE incidence between 1 and 7 months from the start of chemotherapy. The minimal Euclidean distance of the receiver operating characteristic curve was used to derive optimal cut-offs for GDF-15 and NT-proBNP given there was no evidence of a commonly used cut-off. Logistic and Fine and Gray competing risk regression analyses were used to calculate odds ratios (ORs) and subdistribution hazard ratios, respectively, while adjusting for age, sex, anticoagulation, and antiplatelet therapy. We tested in two groups: all patients (n = 476, Model 1) and all patients with nonprimary brain cancers (n = 454, Model 2). In models 1 and 2, GDF-15 ≥2,290.9 pg/mL had adjusted ORs for VTE of 1.65 (95% confidence interval [CI]: 0.89-3.08), and 2.28 (95% CI: 1.28-4.09), respectively. hs-TnT ≥14.0 pg/mL was associated with higher odds of VTE in models 1 and 2 (adjusted ORs: 2.26 [95% CI: 1.40-3.65] and 2.03 [95% CI: 1.07-3.84], respectively). For NT-proBNP, levels ≥183.5 pg/mL were not associated with VTE. Similar results were observed in the Fine and Gray analysis. Our results indicate that increased GDF-15 and hs-TnT levels predicted increased VTE risk.

Comparison of Ticagrelor vs Clopidogrel in Addition to Aspirin in Patients With Minor Ischemic Stroke and Transient Ischemic Attack: A Network Meta-analysis.

Importance: Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective in preventing recurrent strokes after minor ischemic stroke or transient ischemic attack (TIA). However, there is emerging evidence for the use of ticagrelor and aspirin, and the 2 DAPT regimens have not been compared directly. Objective: To compare ticagrelor and aspirin with clopidogrel and aspirin in patients with acute minor ischemic stroke or TIA in the prevention of recurrent strokes or death. Data Sources: MEDLINE, Embase, and Cochrane from database inception until February 2021. Study Selection: Randomized clinical trials that enrolled adults with acute minor ischemic stroke or TIA and provided the mentioned interventions within 72 hours of symptom onset, with a minimum follow-up of 30 days. Data Extraction and Synthesis: PRISMA guidelines for network meta-analyses were followed. Two reviewers independently extracted data and appraised risk of bias. Fixed-effects models were fit using a bayesian approach to network meta-analysis. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank curve plots were produced. Main Outcomes and Measures: The primary outcome was a composite of recurrent stroke or death up to 90 days. Secondary outcomes include major bleeding, mortality, adverse events, and functional disability. A sensitivity analysis was performed at 30 days for the primary outcome. Results: A total of 4014 citations were screened; 5 randomized clinical trials were included. Data from 22 098 patients were analyzed, including 5517 in the clopidogrel and aspirin arm, 5859 in the ticagrelor and aspirin arm, and 10 722 in the aspirin arm. Both clopidogrel and aspirin (HR, 0.74; 95% CrI, 0.65-0.84) and ticagrelor and aspirin (HR, 0.79; 95% CrI, 0.68-0.91) were superior to aspirin in the prevention of recurrent stroke and death. There was no statistically significant difference between clopidogrel and aspirin compared with ticagrelor and aspirin (HR, 0.94; 95% CrI, 0.78-1.13). Both DAPT regimens had higher rates of major hemorrhage than aspirin alone. Clopidogrel and aspirin was associated with a decreased risk of functional disability compared with aspirin alone (HR, 0.82; 95% CrI, 0.74-0.91) and ticagrelor and aspirin (HR, 0.85; 95% CrI, 0.75-0.97). Conclusions and Relevance: DAPT combining aspirin with either ticagrelor or clopidogrel was superior to aspirin alone, but there was no statistically significant difference found between the 2 regimens for the primary outcome.

Life dissatisfaction in Canadians aged 40 and above with cancer and mental health disorders: A cross-sectional study using the Canadian Community Health Survey.

BACKGROUND: Life dissatisfaction varies with different factors--particularly in the presence of chronic conditions, such as cancer. The combination of cancer and mental health disorders may increase life dissatisfaction due to lowered resilience against stress. We sought to determine if life dissatisfaction is higher in Canadians aged 40 and above with cancer compared to the cancer-free population and if there is a synergistic effect between cancer and mental health disorder on life dissatisfaction. METHODS: We conducted a cross-sectional study using the 2015-2016 Canadian Community Health Survey. We included 67,294 subjects aged 40+, and evaluated the association between cancer, mental health disorders, and life dissatisfaction using logistic regression and odds ratios (ORs) while adjusting for age, sex, marital status, education level, and chronic conditions. Relative excess risk due to interaction (RERI), attributional proportion due to interaction (AP), and Synergy index (S-index), were calculated to determine the significance of additive interaction. RESULTS: Compared to the cancer-free population, life dissatisfaction was higher in patients with cancer (OR 2.44, 95% CI: 1.88-3.16) and mental health disorders (OR 5.17, 95% CI: 4.56-5.85). The adjusted ORs for life dissatisfaction were 2.45 (95% CI: 1.74-3.43) and 5.17 (95% CI: 4.55-5.87) for cancer and mental health disorders, respectively, but when both conditions were present, the OR increased to 12.50 (95% CI: 8.40-18.62). The results suggested a synergistic interaction (RERI: 5.89 [95% CI: 0.91-10.87]; AP: 0.47 [95% CI: 0.25-0.69]; and S-index: 2.05 [95% CI: 1.30-3.23]). CONCLUSION: This study showed higher life dissatisfaction in cancer and mental health disorder patients. A synergistic effect was detected between cancer and mental health disorder on life dissatisfaction. These results suggest cancer patients with mental health disorders require additional support and psychological resources to improve their quality of life.

Incidence of stroke in the first year after diagnosis of cancer-A protocol for systematic review and meta-analysis.

INTRODUCTION: There is an increased risk of stroke in patients with cancer-this risk is particularly heightened around the time of cancer diagnosis, although no studies have systematically quantified this risk in the literature. Patients newly diagnosed with cancer without prior stroke represent a highly susceptible population in whom there is a window of opportunity to study and implement primary prevention strategies. Therefore, the objective of this systematic review and meta-analysis is to identify the cumulative incidence of ischemic and hemorrhagic strokes during the first year after a diagnosis of cancer. METHODS AND ANALYSIS: MEDLINE, EMBASE, and PubMed will be searched with the assistance from a medical information specialist, from 1980 until present. Eligible studies will include observational studies that have enrolled adult patients newly diagnosed with cancer and report outcomes of stroke during the first year of cancer diagnosis. We will exclude all randomized and non-randomized interventional studies. Data on participant characteristics, study design, baseline characteristics, and outcome characteristics will be extracted. Study quality will be assessed using the Newcastle-Ottawa Scale for cohort studies, and heterogeneity will be assessed using the I2 statistic. Pooled cumulative incidence will be calculated for ischemic and hemorrhagic strokes separately using a random-effects model. ETHICS AND DISSEMINATION: No formal research ethics approval is necessary as primary data collection will not be done. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will inform clinicians and patients regarding the risk of stroke in patients newly diagnosed with cancer by quantifying the cumulative incidence of each subtype of stroke during the first year after a diagnosis of cancer. This represents a window of opportunity to implement prevention strategies in a susceptible population. REGISTRATION ID WITH OPEN SCIENCE FRAMEWORK: osf.io/ucwy9.

Ticagrelor vs Clopidogrel in addition to Aspirin in minor ischemic stroke/ transient ischemic attack-Protocol for a systematic review and network meta-analysis.

INTRODUCTION: Patients with minor ischemic stroke or transient ischemic attack represent a high-risk population for recurrent stroke. No direct comparison exists comparing dual antiplatelet therapy regimens-namely, Ticagrelor and Aspirin versus Clopidogrel and Aspirin. This systematic review and network meta-analysis (NMA) will examine the efficacy of these two different antiplatelet regimens in preventing recurrent stroke and mortality up to 30 days. METHODS AND ANALYSIS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched with the assistance of a medical information specialist. Two independent reviewers will screen studies for inclusion; eligible studies will include randomized controlled trials that enrolled adults presenting with acute minor ischemic stroke or transient ischemic attack and compared one or more of the interventions against each other and/or a control. The primary outcomes will be recurrent ischemic stroke up to 30 days from symptom onset. Secondary outcomes will include safety outcomes (I.e. major bleeding and mortality), functional disability, and outcomes up to 90 days from symptom onset. A Bayesian approach to NMA will be implemented using the BUGSnet function in R Software. Between group comparisons for time-to-event (TTE) and dichotomous outcomes will be presented in terms of hazard ratios and odds ratios with 95% credible intervals, respectively. Secondary effect measures of treatment ranking will also be estimated. ETHICS AND DISSEMINATION: No formal research ethics approval are necessary. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will aid clinicians in decision-making on the choice of antithrombotic therapy in a high-risk stroke population and could be important in the development of future treatment trials and guidelines. Registration ID with Open Science Framework: 10.17605/OSF.IO/XDJYZ.