Carl Chartrand-Lefebvre

Persistence of HIV antigens may drive chronic inflammation, leading to early-onset comorbidity among people living with HIV. We found that the presence of soluble glycoprotein 120 in plasma is associated with increased coronary inflammation, as measured by the pericoronary fat attenuation index (PFAI), a predictor of overt cardiovascular disease.

Antiretroviral therapy (ART) controls HIV-1 replication in people with HIV-1 (PWH), but intestinal integrity impairment persists and fuels microbial translocation and chronic immune activation, thus heightening the cardiovascular disease (CVD) risk. Here, we sought to identify novel immunological correlates of the HIV and CVD status in ART-treated PWH (HIV⁺; n = 42) and uninfected participants (HIV⁻; n = 40) of the Canadian HIV and Aging Cohort Study (CHACS), with/without subclinical coronary atherosclerotic plaques, measured by Coronary Computed Tomography Angiography as total plaque volume (TPV, mm³). PBMCs were analyzed by flow cytometry for the expression of T-cell lineage (CD45, CD3, CD4, CD8αα, CD8αβ, TCRαβ, TCRγδ), epithelial cell (EpCAM/CD326), activation (HLA-DR), and gut-homing/residency markers (CD69, CD196/CCR6, CD199/CCR9, CD49d/Itgα4, CD103/ItgαE, Itgβ7). Alterations in the CD3⁺ T-cell pool, such as increased frequencies of CD8⁺TCRαβ⁺ and TCRγδ⁺ cells, to the detriment of CD4⁺TCRαβ⁺ subsets, were associated with the HIV status. Also, CD4⁺ T-cells with CD326⁺CD69⁺CCR6⁺ItgαE⁺ and CCR6⁺Itgβ7⁻ phenotypes were increased in frequency in HIV⁺ vs. HIV⁻ participants, together with a decreased frequency of CD8⁺ T-cells with an intraepithelial lymphocyte (IEL)-like CD3⁺CD4⁻TCRαβ⁺TCRγδ⁻CD8αα⁺CD8αβ⁻ phenotype. Finally, multivariate logistic regression identified the frequency of ItgαE⁺CD8⁺, ItgαE⁻CD8⁺, CCR6⁺CD4⁺, and CCR6⁺Itgβ7⁻CD4⁺ T-cells as strong positive correlates of HIV status and atherosclerotic plaque in ART-treated PWH.

People with HIV (PWH) have an increased risk of developing cardiovascular disease (CVD). Our recent data demonstrated that the multi-isoform proinflammatory cytokine IL-32 is upregulated in PWH and is associated with arterial stiffness and subclinical atherosclerosis. However, the mechanisms by which IL-32 contributes to the pathogenesis of these diseases remain unclear. Here, we show that while the less expressed IL-32α isoform induces the differentiation of human classical monocytes into the calcium-resorbing osteoclast cells, the dominantly expressed isoforms IL-32β and IL-32γ suppress this function through the inhibition of TGF-β and induce the differentiation of monocytes into the calcium-depositing osteocalcin+ osteoblasts. These results aligned with the increase in plasma levels of osteoprotegerin, a biomarker of vascular calcification, and its association with the presence of coronary artery subclinical atherosclerosis and calcium score in PWH. These findings support a novel role for the proinflammatory cytokine IL-32 in the pathophysiology of CVD by increasing vascular calcification in PWH.

Cardiovascular disease (CVD) remains an important comorbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed in the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) > 5%) revealed a 2–3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by computed tomography angiography scan (CTAScan) as the total (TPV) and low attenuated plaque volume (LAPV), in ART-treated PLWH (HIV+) versus uninfected controls (HIV−). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4⁺ T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1, and triglyceride levels; lower Th17/Treg ratios; and classical monocyte expansion. Among HIV⁺, TPV⁺ versus TPV⁻ exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9^lowHLADR^high monocytes, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9^lowHLADR^high monocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.

Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic roles of the different IL-32 isoforms in CVD are yet to be identified. In this study, we aimed to investigate the potential impact of IL-32 isoforms on coronary artery endothelial cells (CAEC), whose dysfunction represents a major factor for atherosclerosis. Our results demonstrated that the predominantly expressed IL-32 isoforms (IL-32β and IL-32γ) have a selective impact on the production of the proinflammatory cytokine IL-6 by CAEC. Furthermore, these two isoforms induced endothelial cell dysfunction by upregulating the expression of the adhesion molecules ICAM-I and VCAM-I and the chemoattractants CCL-2, CXCL-8 and CXCL-1. IL-32-mediated expression of these chemokines was sufficient to drive monocyte transmigration in vitro. Finally, we demonstrate that IL-32 expression in both PLWH and controls correlates with the carotid artery stiffness, measured by the cumulated lateral translation. These results suggest a role for IL-32-mediated endothelial cell dysfunction in dysregulation of the blood vessel wall and that IL-32 may represent a therapeutic target to prevent CVD in PLWH.

Purpose: Coronary bioresorbable stents (BRS) do not produce blooming artifacts on computed tomography (CT), in contrast to metallic stents, as they are made of a bioresorbable polymer and are radiolucent. They allow to evaluate the coronary plaque beneath. The low-attenuation plaque (LAP) suggests plaque vulnerability and is CT assessable. The aim of our study was to show the possibility of a non-invasive CT evaluation of the volume and the LAP composition of the intra- and juxta-stent plaque. Methodology: In our prospective longitudinal study, we recruited 27 consecutive patients (35 BRS stents total; mean age 60 +/- 9 years) with bioresorbable stents for a 256-slice ECG-synchronized CT evaluation at 1- and 12-months post stent implantation. Total plaque volume (mm3), absolute and relative (%) LAP volume per block in the pre- intra- and post-stent zones were analyzed; comparison 1- and 12-months post-implantation of BRS. Changes in the previously mentioned variables were assessed by the mixed effects models with and without spline, which also accounted for the correlation between repeated measurements. Results: Our block or spline model analysis has shown no significant difference in plaque or absolute LAP volumes in pre- intra- and post-stent zones between 1 and 12 months. Interestingly, % LAP volume increases near-significantly in the distal block of the intrastent at 12-mo follow-up (from 23.38 ± 1.80% to 26.90 ± 2.22% (increase of 15%), p = 0.052). Conclusion: Our study demonstrates the feasibility of the repeated non-invasive quantitative analysis of the intrastent coronary plaque and of the in-stent lumen by CT scan.

The objective of this study was to evaluate whether adaptive NKG2C⁺CD57⁺ natural killer (adapNK) cell frequencies are associated with pre-clinical coronary atherosclerosis in participants of the Canadian HIV and Aging Cohort Study. This cross-sectional study included 194 Canadian HIV and Aging Cohort Study participants aged ≥ 40 years of which 128 were cytomegalovirus (CMV)⁺ people living with HIV (PLWH), 8 were CMV⁻PLWH, 37 were CMV mono-infected individuals, and 21 were neither human immunodeficiency virus nor CMV infected. Participants were evaluated for the frequency of their adapNK cells and total plaque volume (TPV). TPV was assessed using cardiac computed tomography. Participants were classified as free of, or having, coronary atherosclerosis if their TPV was “0” and ">0,” respectively. The frequency of adapNK cells was categorized as low, intermediate or high if they constituted 20%, respectively, of the total frequency of CD3⁻CD56^dim NK cells. The association between adapNK cell frequency and TPV was assessed using an adjusted Poisson regression analysis. A greater proportion of CMV⁺PLWH with TPV = 0 had high adapNK cell frequencies than those with TPV > 0 (61.90% vs 39.53%, P = .03) with a similar non-significant trend for CMV mono-infected participants (46.15% vs 34.78%). The frequency of adapNK cells was negatively correlated with TPV. A high frequency of adapNK cells was associated with a relative risk of 0.75 (95% confidence intervals 0.58, 0.97, P = .03) for presence of coronary atherosclerosis. This observation suggests that adapNK cells play a protective role in the development of coronary atherosclerotic plaques.

BACKGROUND We aimed to evaluate the feasibility of implementing Chester, a novel web-based chest X-ray (CXR) interpretation artificial intelligence (AI) tool, in the medical education curriculum and explore its effect on the diagnostic performance of undergraduate medical students. METHODS Third-year trainees were randomized in experimental (N=16) and control (N=16) groups and stratified for age, gender, confidence in CXR interpretation, and prior experience. Participants filled a pre-intervention survey, a test exam (Exam1), a final exam (Exam2), and a post-intervention survey. The experimental group was allowed to use Chester during Exam1 while the control group could not. All participants were forbidden from using any resources during Exam2. The diagnostic interpretation of a fellowship-trained chest radiologist was used as the standard of reference. Chester’s performance on Exam1 was 60%. A five-point Likert scale was used to assess students’ perceived confidence before/after the exams as well as Chester’s perceived usefulness. RESULTS Using a mixed model for repeated measures (MMRM), it was found that Chester did not have a statistically significant impact on the experimental group’s diagnostic performance nor confidence level when compared to the control group. The experimental group rated Chester’s usefulness at 3.7/5, its convenience at 4.25/5, and their likelihood to reuse it at 4.1/5. CONCLUSION Our experience highlights the interest of medical students in using AI tools as educational resources. While the results of the pilot project are inconclusive for now, they demonstrate proof of concept for a repeat experiment with a larger sample and establish a robust methodology to evaluate AI tools in radiological education. Finally, we believe that additional research should be focused on the applications of AI in medical education so students understand this new technology for themselves and given the growing trend of remote learning.

Noncalcified coronary plaque burden at coronary CT angiography was two- to threefold higher in people living with HIV compared with healthy volunteers without HIV. Background People living with HIV (PLWH) have a higher risk of myocardial infarction. Coronary atherosclerotic plaque CT characterization helps to predict cardiovascular risk. Purpose To measure CT...