14 research outputs found

    Risk of incident atrial fibrillation in patients presenting with retinal artery or vein occlusion:a nationwide cohort study

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    Abstract Background The inter-relationships of atrial fibrillation (AF) to retinal vascular occlusions (whether retinal artery occlusion (RAO) or retinal venous occlusion (RVO)) remain unclear. It is unknown if a presentation of retinal artery or venous occlusions may indicate a new onset cardiac arrhythmia. To shed light on this association, we investigated the risk of new onset AF in patients with known RAO and RVO. Methods Patients with retinal occlusions from 1997 to 2011 were identified through Danish nationwide registries and matched 1:5 according to sex and age. Cumulative incidence and unadjusted rates of AF according to retinal vascular occlusions (i.e. RAO or RVO) were determined. Hazard ratios (HR) of AF according to retinal vascular occlusion were adjusted for hypertension, diabetes, vascular disease and prior stroke/systemic thromboembolism/transient ischemic attack. Results One thousand three hundred sixty-eight cases with retinal vascular occlusions were identified (median age 71.4 (inter quartile range (IQR); 61.2–79.8), 47.3% male). RAO constituted 706 cases (51.6%) and RVO 529 (38.7%). The rate of incident AF amongst all cases with retinal vascular occlusion was 1.74 per 100 person-years (95% confidence interval (CI), 1.47–2.06) compared to 1.22 (95% CI, 1.12–1.33) in the matched control group. The rate of AF in RAO was 2.01 (95% CI, 1.6–2.52) and 1.52 (1.15–2.01) in RVO. HRs of incident AF adjusted for cardiovascular comorbidities were 1.26 (95% CI; 1.04–1.53, p = 0.019) for any retinal vascular occlusion, 1.45 (95% CI; 1.10–1.89, p = 0.015) for RAO, and 1.02 (95% CI; 0.74–1.39, p = 0.920) for RVO. Conclusions A new diagnosis of retinal vascular occlusion in patients without prior AF was associated with increased risk of incident AF, particularly amongst patients with RAO. Awareness of AF in patients with retinal vascular occlusions is advised

    Clinical outcomes in patients with multi-hit TP53 chronic lymphocytic leukemia treated with ibrutinib

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    PURPOSE: TP53 aberration (TP53 mutation and/or 17p deletion) is the most important predictive marker in chronic lymphocytic leukemia (CLL). While each TP53 aberration is considered an equal prognosticator, the prognostic value of carrying isolated (single-hit) or multiple (multi-hit) TP53 aberrations remains unclear, particularly in the context of targeted agents. EXPERIMENTAL DESIGN: We performed deep sequencing of TP53 using baseline samples collected from 51 TP53 aberrant patients treated with ibrutinib in a phase II study (NCT01500733). RESULTS: We identified TP53 mutations in 43 patients (84%) and del(17p) in 47 (92%); 9 and 42 patients carried single-hit and multi-hit TP53, respectively. The multi-hit TP53 subgroup was enriched with younger patients who had prior treatments and unmutated immunoglobulin heavy-chain variable region gene. We observed significantly shorter overall survival, progression-free survival (PFS), and time-to-progression (TTP) in patients with multi-hit TP53 compared with those with single-hit TP53. Clinical outcomes were similar in patient subgroups stratified by 2 or >2 TP53 aberrations. In multivariable analyses, multi-hit TP53 CLL was independently associated with inferior PFS and TTP. In sensitivity analyses, excluding mutations below 1% VAF demonstrated similar outcome. Results were validated in an independent population-based cohort of 112 CLL patients treated with ibrutinib. CONCLUSIONS: In this study, single-hit TP53 defines a distinct subgroup of patients with an excellent long-term response to single-agent ibrutinib, while multi-hit TP53 is independently associated with shorter PFS. These results warrant further investigations on prognostication and management of multi-hit TP53 CLL

    Capture and Detection of Circulating Glioma Cells Using the Recombinant VAR2CSA Malaria Protein

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    Diffuse gliomas are the most common primary malignant brain tumor. Although extracranial metastases are rarely observed, recent studies have shown the presence of circulating tumor cells (CTCs) in the blood of glioma patients, confirming that a subset of tumor cells are capable of entering the circulation. The isolation and characterization of CTCs could provide a non-invasive method for repeated analysis of the mutational and phenotypic state of the tumor during the course of disease. However, the efficient detection of glioma CTCs has proven to be challenging due to the lack of consistently expressed tumor markers and high inter- and intra-tumor heterogeneity. Thus, for this field to progress, an omnipresent but specific marker of glioma CTCs is required. In this article, we demonstrate how the recombinant malaria VAR2CSA protein (rVAR2) can be used for the capture and detection of glioma cell lines that are spiked into blood through binding to a cancer-specific oncofetal chondroitin sulfate (ofCS). When using rVAR2 pull-down from glioma cells, we identified a panel of proteoglycans, known to be essential for glioma progression. Finally, the clinical feasibility of this work is supported by the rVAR2-based isolation and detection of CTCs from glioma patient blood samples, which highlights ofCS as a potential clinical target for CTC isolation.Medicine, Faculty ofOther UBCNon UBCUrologic Sciences, Department ofReviewedFacult

    Risk of incident atrial fibrillation in patients presenting with retinal artery or vein occlusion: a nationwide cohort study

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    Abstract Background The inter-relationships of atrial fibrillation (AF) to retinal vascular occlusions (whether retinal artery occlusion (RAO) or retinal venous occlusion (RVO)) remain unclear. It is unknown if a presentation of retinal artery or venous occlusions may indicate a new onset cardiac arrhythmia. To shed light on this association, we investigated the risk of new onset AF in patients with known RAO and RVO. Methods Patients with retinal occlusions from 1997 to 2011 were identified through Danish nationwide registries and matched 1:5 according to sex and age. Cumulative incidence and unadjusted rates of AF according to retinal vascular occlusions (i.e. RAO or RVO) were determined. Hazard ratios (HR) of AF according to retinal vascular occlusion were adjusted for hypertension, diabetes, vascular disease and prior stroke/systemic thromboembolism/transient ischemic attack. Results One thousand three hundred sixty-eight cases with retinal vascular occlusions were identified (median age 71.4 (inter quartile range (IQR); 61.2–79.8), 47.3% male). RAO constituted 706 cases (51.6%) and RVO 529 (38.7%). The rate of incident AF amongst all cases with retinal vascular occlusion was 1.74 per 100 person-years (95% confidence interval (CI), 1.47–2.06) compared to 1.22 (95% CI, 1.12–1.33) in the matched control group. The rate of AF in RAO was 2.01 (95% CI, 1.6–2.52) and 1.52 (1.15–2.01) in RVO. HRs of incident AF adjusted for cardiovascular comorbidities were 1.26 (95% CI; 1.04–1.53, p = 0.019) for any retinal vascular occlusion, 1.45 (95% CI; 1.10–1.89, p = 0.015) for RAO, and 1.02 (95% CI; 0.74–1.39, p = 0.920) for RVO. Conclusions A new diagnosis of retinal vascular occlusion in patients without prior AF was associated with increased risk of incident AF, particularly amongst patients with RAO. Awareness of AF in patients with retinal vascular occlusions is advised
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