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This randomized controlled trial compared the effects of home-based exercise, with or without cognitive training, on cognition and physical function in individuals aged 50 years and older with stable CVD during the COVID-19 pandemic. 122 patients (67.3 ± 7.9 years, 71% men) with stable CVD (77% coronary heart disease) were randomly assigned (1:1) to (1) Home-based physical exercise alone, or (2) Home-based physical exercise combined with cognitive training. Cognition (executive functions (primary outcome), processing speed, episodic memory, and working memory) and physical functions were assessed remotely at baseline, 3 months, and 6 months. Adjusted mean changes from baseline to 3 months and 6 months for executive functions, episodic memory, working memory, sit-to-stand test, gait speed, and timed up-and-go test were significant in the overall sample (p < 0.05). Furthermore, executive functions, episodic memory, sit-to-stand test, and timed up-and-go performances were significantly improved at 6 months in both groups when analyzed separately although no group differences were observed. Mean exercise dose differed significantly between the 2 groups: 1413 vs 953 METs.min -1  week -1 respectively for the exercise and combined group (p < 0.01). Mean cognitive training duration was 25.6 ± 16.6 min.week -1 for the combined intervention group. Results remained unchanged after accounting for the exercise dose. In adults affected by CVD, a remote combined intervention integrating sequential cognitive and exercise training yields comparable enhancements in executive function, episodic memory, and physical performances compared to exercise training alone. ClinicalTrials.gov: NCT04661189., Competing Interests: Declarations. Ethics approval and consent to participate: Participants provided written informed consent by email before starting the study. The COVEPICARDIO was conducted in compliance with the International Conference on Harmonization Good Clinical Practice (ICH-GCP) and in accordance with the Helsinki Declaration. The study protocol was approved by the Montreal Heart Institute’s (MHI) Research Ethics Board (FWA00003235; research project: ICM 2020–2785). Consent for publication: All authors carefully revised the manuscript, and they all approved the final version for publication. Conflict of interest: The authors declare that the research is conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025. The Author(s), under exclusive licence to American Aging Association.)

Background: The 21-gene Breast Recurrence Score (RS) assay, "the assay", has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada., Patients and Methods: We conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes. Physicians completed a questionnaire indicating treatment choice prior to and post availability of RS results. The primary endpoint was change in the physician's recommendation for chemotherapy prior to and post assay results. Secondary endpoints included change in physician's expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results., Results: For the entire cohort, physician recommendation for chemotherapy was reduced by an absolute 67.1% by knowledge of the RS assay result (P < .0001). Physician recommendation of chemotherapy was decreased by 75.9% for patients RS result <14 (P < .0001); and 67.5% for patients with RS result 14-25 (P < .0001). Changes in treatment recommendations were associated with an overall reduction in cost by 73.7% per patient, and after incorporating the cost of the RS test, a cost benefit of $823 CAN at 6-month follow-up., Conclusion: Altogether, we established that the assay led to a two-third reduction in the use of chemotherapy, and was a cost-effective approach for hormone receptor-positive, node-positive breast cancer., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Platelet hyperactivity is deleterious in coronary artery disease (CAD), requiring lifelong antiplatelet therapy, and is associated with worse cognitive outcomes. Upon activation, platelets release Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin protective against cognitive decline. Given these apparently opposing effects of platelet activation on cognitive health, we investigated whether BDNF levels intercede in the relationship between platelet activation and cognitive function; and whether this relationship is moderated by the presence of CAD. Methods: In this cross-sectional study, 1,280 participants with ( n = 673) and without CAD ( n = 607) completed the Montreal Cognitive Assessment (MoCA). Plasma BDNF and soluble P-selectin (a marker of platelet activity) levels were assessed using multiplex flow cytometry. Results: In a mediation model, platelet activity was correlated with higher plasma BDNF concentrations (b = 0.53, p < 0.0001). The relationship between sP-selectin and BDNF concentrations was stronger for individuals without CAD (b = 0.71, p < 0.0001) than for CAD participants (b = 0.43, p < 0.0001; p interaction <0.0001). Higher BDNF concentrations were associated with higher MoCA scores (b = 0.26, p = 0.03). The overall effect of platelet activity on cognitive performance was non-significant (total effect: b = -0.12, p = 0.13), and became significant when accounting for BDNF as a mediating factor (direct effect: b = -0.26, p = 0.01). This resulted in a positive indirect effect of platelet activity (via BDNF) on MoCA scores (b = 0.14, CI 95% 0.02-0.30), that was smaller in CAD participants than in non-CAD participants [Δ -0.07 (95% CI -0.14 to -0.01)]. Conclusions: BDNF released from activated platelets could be a mitigating factor in a negative association between platelet activity and cognitive function., Competing Interests: HC has participated as a site PI in pharmaceutical trial activities in the past 5 years sponsored by: Hoffmann-La Roche Limited, TauRx, Lilly, Anavex Life Sciences, Alector LLC, and Immunocal site investigator for trials; and is Scientific Director for the Canadian Consortium on Neurodegeneration in Aging, which receives partner support from a set of partners including industry: Pfizer Inc., Lilly, and Sanofi. ML has received speaker fees from Bayer; has participated in industry-funded trials from Idorsia; has served on advisory boards for Servier and Orimed Pharma; and has received in-kind and financial support for investigator-initiated grants from Leo Pharma, Roche Diagnostics, Aggredyne, and Fujimori Kogyo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bélanger, Bouchard, Le Blanc, Starnino, Welman, Chabot-Blanchet, Busseuil, Chertkow, D'Antono and Lordkipanidzé.)

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10 -8 ) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10 -8 ) in interaction with colchicine (P = 1.19 × 10 -5 ) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

Background: Targeted temperature management (TTM) has been associated with an improvement in neurological function and survival in patients with cardiac arrest (CA) and an initially shockable rhythm. We report the Montreal Heart Institute (MHI) experience using TTM to evaluate mortality and neurological outcome in patients remaining in coma after CA, regardless of the initial rhythm., Methods: We performed a retrospective review of all patients receiving TTM at the MHI between 2008 and 2015. Primary outcome was a composite of mortality and poor neurological outcome at hospital discharge. We also evaluated the long-term outcomes of those who initially survived to hospital discharge., Results: A total of 147 patients (120 men, mean age 59.5 ± 12.5 years) underwent TTM at the MHI during the study period. Overall survival to hospital discharge with good neurological outcome was 45.6%. Shockable rhythm was associated with a better outcome (mortality odds ratio, 0.212; 95% confidence interval, 0.068-0.664; P  = 0.008). Of the 11 initial survivors with a poor neurological status (Cerebral Performance Category ≥ 3), 4 died rapidly (within 1 month of hospital discharge), but 6 (54.5%) markedly improved their neurological status to Cerebral Performance Category 1. Long-term survival (mean follow-up of 38 ± 26 months) for those alive at hospital discharge (n = 76 patients) was 81.9%., Conclusion: Our retrospective analysis of CA survivors treated with TTM at MHI showed good survival, similar to the published results from the landmark randomized controlled trials, despite enrolling patients with nonshockable rhythms. A significant proportion of survivors with poor neurological outcome at discharge improved at follow-up., (© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc.)

Background: Comorbidity indexes derived from administrative databases are essential tools of research in global health. We sought to develop and validate a novel cardiac-specific comorbidity index, and to compare its accuracy with the generic Charlson-Deyo and Elixhauser comorbidity indexes., Methods: We derived the cardiac-specific comorbidity index from consecutive patients who were admitted to hospital at a tertiary-care cardiology hospital in Quebec. We used logistic regression analysis and incorporated age, sex and 22 clinically relevant comorbidities to build the index. We compared the cardiac-specific comorbidity index with refitted Charlson-Deyo and Elixhauser comorbidity indexes using the C-statistic and net reclassification improvement to predict in-hospital death, and the Akaike information criterion to predict length of stay. We validated our findings externally in an independent cohort obtained from a provincial registry of coronary disease in Alberta., Results: The novel cardiac-specific comorbidity index outperformed the refitted generic Charlson-Deyo and Elixhauser comorbidity indexes for predicting in-hospital mortality in the derivation population ( n = 10 137): C-statistic 0.95 (95% confidence interval [CI] 0.94-0.9) v. 0.81 (95% CI 0.77-0.84) and 0.86 (95% CI 0.82-0.89), respectively. In the validation population ( n = 17 877), the cardiac-specific comorbidity index was similarly better: C-statistic 0.92 (95% CI 0.89-0.94) v. 0.76 (95% CI 0.71-0.81) and 0.82 (95% CI 0.78-0.86), respectively, and also numerically outperformed the Charlson-Deyo and Elixhauser comorbidity indexes for predicting 1-year mortality (C-statistic 0.78 [95% CI 0.76-0.80] v. 0.75 [95% CI 0.73-0.77] and 0.77 [95% CI 0.75-0.79], respectively). Similarly, the cardiac-specific comorbidity index showed better fit for the prediction of length of stay. The net reclassification improvement using the cardiac-specific comorbidity index for the prediction of death was 0.290 compared with the Charlson-Deyo comorbidity index and 0.192 compared with the Elixhauser comorbidity index., Interpretation: The cardiac-specific comorbidity index predicted in-hospital and 1-year death and length of stay in cardiovascular populations better than existing generic models. This novel index may be useful for research of cardiology outcomes performed with large administrative databases., Competing Interests: Competing interests: Stephen Wilton has received consultant fees from Arca Biopharma and research grants from Medtronic of Canada, Abbott and Boston Scientific. No other competing interests were declared. This article has been peer reviewed., (© 2019 Joule Inc. or its licensors.)

Vascular inflammation is increased in patients with psoriasis. This randomized, double-blind, multicenter study evaluated the effects of tumor necrosis factor-α antagonist adalimumab on vascular inflammation in patients with psoriasis. A total of 107 patients were randomized (1:1) to receive adalimumab for 52 weeks or placebo for 16 weeks followed by adalimumab for 52 weeks. Vascular inflammation was assessed with positron emission tomography-computed tomography. There were no differences in the change from baseline in vessel wall target-to-background ratio (TBR) from the ascending aorta (primary endpoint) (adalimumab: TBR = 0.002, 95% confidence interval [CI] = -0.048 to 0.053; placebo: TBR = -0.002, 95% CI = -0.053 to 0.049; P = 0.916) and the carotids (adalimumab: TBR = 0.031, 95% CI = -0.005 to 0.066; placebo: TBR = 0.018, 95% CI = -0.019 to 0.055; P = 0.629) at week 16 between adalimumab and placebo. After 52 weeks of treatment with adalimumab there was no significant change from start of treatment in TBR from the ascending aorta (TBR = -0.006, 95% CI = -0.049 to 0.038; P = 0.796), but there was an increase in TBR in carotids (TBR = 0.027, 95% CI = 0.000 to 0.054; P = 0.046). This study showed no difference over 16 weeks in vascular inflammation in patients treated with a tumor necrosis factor-α antagonist or placebo and a modest increase in vascular inflammation in carotids after 52 weeks of treatment with adalimumab., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS., Methods and Findings: The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6-7 weeks (i.e. 2-3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was reduced (-32.9%) in controls (p = 0.017 between groups). The level of circulating SDF-1 (stromal cell-derived factor-1), a chemokine involved in progenitor cell recruitment, increased significantly (change of 21.5%) in controls, while it remained unchanged in CSL-111-treated patients (p = 0.031 between groups). In vitro exposure to CSL-111 of early EPC isolated from healthy volunteers significantly increased CD34+ cells, reduced early EPC apoptosis and enhanced their migration capacity towards SDF-1., Conclusions: The relative increase in circulating CD34+ cells and the low SDF-1 levels observed following rHDL infusions in ACS patients point towards a role of rHDL in cardiovascular repair mechanisms., Competing Interests: The compound used in the present study was a gift of CSL Limited (Parkville, Australia). We confirm that this commercial funding does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: The purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular access site complications (VASC) at a population level when femoral access (FA) is performed., Background: The recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted., Methods: Logistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used. We calculated the adjusted attributable risk to estimate the proportion of VASC attributable to the introduction of RA in FA patients of the contemporary cohort., Results: A total of 17,059 patients were included. At a population level, the VASC rate was higher in the overall contemporary cohort compared with the historical cohort (adjusted rates: 2.91% vs. 1.98%; odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.17 to 1.89; p = 0.001). In the contemporary cohort, RA patients experienced fewer VASC than FA patients (adjusted rates: 1.44% vs. 4.19%; OR: 0.33, 95% CI: 0.23 to 0.48; p < 0.001). We observed a higher VASC rate in FA patients in the contemporary cohort compared with the historical cohort (adjusted rates: 4.19% vs. 1.98%; OR: 2.16, 95% CI: 1.67 to 2.81; p < 0.001). This finding was consistent for both diagnostic and therapeutic catheterizations separately. The proportion of VASCs attributable to RA in the contemporary FA patients was estimated at 52.7%., Conclusions: In a contemporary population where both RA and FA were used, the safety benefit associated with RA is offset by a paradoxical increase in VASCs among FA patients. The existence of this radial paradox should be taken into consideration, especially among trainees and default radial operators., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background. Changes in cardiopulmonary reserve and biomarkers related to wall stress, inflammation, and oxidative stress concomitantly with the evaluation of peripheral arterial blood flow have not been investigated in patients with heart failure with preserved ejection fraction (HFpEF) compared with healthy subjects (CTL). Methods and Results. Eighteen HFpEF patients and 14 CTL were recruited. Plasma levels of inflammatory and oxidative stress biomarkers were measured at rest. Brain natriuretic peptide (BNP) was measured at rest and peak exercise. Cardiopulmonary reserve was assessed using an exercise protocol with gas exchange analyses. Peripheral arterial blood flow was determined by strain gauge plethysmography. Peak VO2 (12.0 ± 0.4 versus 19.1 ± 1.1 mL/min/kg, P < 0.001) and oxygen uptake efficiency slope (1.55 ± 0.12 versus 2.06 ± 0.14, P < 0.05) were significantly decreased in HFpEF patients compared with CTL. BNP at rest and following stress, C-reactive-protein, interleukin-6, and TBARS were significantly elevated in HFpEF. Both basal and posthyperemic arterial blood flow were not significantly different between the HFpEF patients and CTL. Conclusions. HFpEF exhibits a severe reduction in cardiopulmonary reserve and oxygen uptake efficiency concomitantly with an elevation in a broad spectrum of biomarkers confirming an inflammatory and prooxidative status in patients with HFpEF.