Gender Differences in Pharmacokinetics: A Perspective on Contrast Agents.

Gender is an important risk factor for adverse drug reactions. Women report significantly more adverse drug reactions than men. There is a growing consensus that gender differences in drug PK is a main contributor to higher drug toxicity in women. These differences stem from physiological differences (body composition, plasma protein concentrations, and liver and kidney function), drug interactions, and comorbidities. Contrast agents are widely used to enhance diagnostic performance in computed tomography and magnetic resonance imaging. Despite their broad use, these contrast agents can lead to important adverse reactions including hypersensitivity reactions, nephropathy, and hyperthyroidism. Importantly, female gender is one of the main risk factors for contrast agent toxicity. As these adverse reactions may be related to gender differences in PK, this perspective aims to describe distribution and elimination pathways of commonly used contrast agents and to critically discuss gender differences in these processes.

Alterations in Th17 Cells and Non-Classical Monocytes as a Signature of Subclinical Coronary Artery Atherosclerosis during ART-Treated HIV-1 Infection.

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 CCR9lowHLADRhigh monocytes, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhigh 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.

Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy-Treated Individuals With Undetectable Viremia.

BACKGROUND: Chronic inflammation persists in some people living with human immunodeficiency virus (HIV) during antiretroviral therapy and is associated with premature aging. The glycoprotein 120 (gp120) subunit of HIV-1 envelope sheds and can be detected in plasma, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasma soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, linked to CD4 depletion in vitro, contribute to chronic inflammation, immune dysfunction, and subclinical cardiovascular disease in participants of the Canadian HIV and Aging Cohort Study with undetectable viremia. METHODS: Cross-sectional assessment of sgp120 and anti-cluster A antibodies was performed in 386 individuals from the cohort. Their association with proinflammatory cytokines and subclinical coronary artery disease was assessed using linear regression models. RESULTS: High levels of sgp120 and anti-cluster A antibodies were inversely correlated with CD4+ T cell count and CD4/CD8 ratio. The presence of sgp120 was associated with increased levels of interleukin 6. In participants with detectable atherosclerotic plaque and detectable sgp120, anti-cluster A antibodies and their combination with sgp120 levels correlated positively with the total volume of atherosclerotic plaques. CONCLUSIONS: This study showed that sgp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of people living with HIV, contributing to the development of premature comorbid conditions.

Transarterial Embolization of Simple Pulmonary Arteriovenous Malformations: Long-Term Outcomes of 0.018-Inch Coils versus Vascular Plugs.

PURPOSE: To compare the safety, effectiveness, and persistence rates of 0.018-inch coils with those of Amplatzer vascular plugs (AVPs; Abbott Vascular, Abbott Park, Illinois) for the treatment of pulmonary arteriovenous malformations (PAVMs) in response to a growing concern that 0.018-inch coil embolization would increase the long-term persistence rate. MATERIALS AND METHODS: This is a retrospective, single-center study of a database (2002-2020) of 633 PAVM embolizations. Complex PAVMs and those not embolized with 0.018-inch coils or plugs were excluded. PAVM embolization material was classified into 4 groups: (a) 0.018-inch nonfibered coils (NFCs), (b) 0.018-inch fibered coils (FCs), (c) NFCs and FCs, or (d) plugs. Persistence was defined as flow through the PAVM on digital subtraction angiography (DSA) or as <30% diameter reduction of the aneurysmal sac on unenhanced computed tomography (CT). Kaplan-Meier analysis and Cox regression were used to assess PAVM's persistence-free survival. RESULTS: A total of 312 PAVM embolizations with NFCs (43 PAVMs), FCs (127 PAVMs), NFCs and FCs (12 PAVMs), or plugs (130 PAVMs) in 109 patients (28% men; mean age = 49 years) were included. All PAVM embolizations were technically successful without any major adverse events. PAVM persistence-free survival rates at 10 years' follow-up were 40.8% versus 44.7% in the NFC and FC groups (P = .22) and 47.3% versus 81.0% in the 0.018-inch coil (NFC or FC) and plug groups (P < .0001), respectively. There were 0.43 (79/182) and 0.08 (10/130) re-embolization procedures per PAVM in the 0.018-inch coil and plug groups, respectively (P < .001). CONCLUSIONS: PAVM embolization with 0.018-inch coils was safe, but persistence rate with PAVM embolization was significantly higher than that with plugs, with no significant differences between FCs and NFCs.

IL-32 Drives the Differentiation of Cardiotropic CD4+ T Cells Carrying HIV DNA in People With HIV.

Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms ß and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH.

CT analysis of aortic calcifications to predict abdominal aortic aneurysm rupture.

BACKGROUND: Abdominal aortic aneurysm (AAA) rupture prediction based on sex and diameter could be improved. The goal was to assess whether aortic calcification distribution could better predict AAA rupture through machine learning and LASSO regression. METHODOLOGY: In this retrospective study, 80 patients treated for a ruptured AAA between January 2001 and August 2018 were matched with 80 non-ruptured patients based on maximal AAA diameter, age, and sex. Calcification volume and dispersion, morphologic, and clinical variables were compared between both groups using a univariable analysis with p = 0.05 and multivariable analysis through machine learning and LASSO regression. We used AUC for machine learning and odds ratios for regression to measure performance. RESULTS: Mean age of patients was 74.0 ± 8.4 years and 89% were men. AAA diameters were equivalent in both groups (80.9 ± 17.5 vs 79.0 ± 17.3 mm, p = 0.505). Ruptured aneurysms contained a smaller number of calcification aggregates (18.0 ± 17.9 vs 25.6 ± 18.9, p = 0.010) and were less likely to have a proximal neck (45.0% vs 76.3%, p < 0.001). In the machine learning analysis, 5 variables were associated to AAA rupture: proximal neck, antiplatelet use, calcification number, Euclidian distance between calcifications, and standard deviation of the Euclidian distance. A follow-up LASSO regression was concomitant with the findings of the machine learning analysis regarding calcification dispersion but discordant on calcification number. CONCLUSION: There might be more to AAA calcifications that what is known in the present literature. We need larger prospective studies to investigate if indeed, calcification dispersion affects rupture risk. CLINICAL RELEVANCE STATEMENT: Ruptured aneurysms are possibly more likely to have their calcification volume concentrated in a smaller geographical area. KEY POINTS: • Abdominal aortic aneurysm (AAA) rupture prediction based on sex and diameter could be improved. • For a given calcification volume, AAAs with well-distributed calcification clusters could be less likely to rupture. • A machine learning model including AAA calcifications better predicts rupture compared to a model based solely on maximal diameter and sex alone, although it might be prone to overfitting.

Baseline characteristics of a prospective cohort study of aging and cardiovascular diseases among people living with HIV.

OBJECTIVES: Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol. METHODS: CHACS is a multi-centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow-up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender-gender roles, gender identity, gender relationships, and institutionalized gender-will be measured using the GENESIS-PRAXY questionnaire. Diet will be assessed using a validated, web-based, self-administered food frequency questionnaire. RESULTS: A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50-61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail. CONCLUSIONS: The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio-economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses.

Plasmatic HIV-1 soluble gp120 is associated with immune dysfunction and inflammation in ART-treated individuals with undetectable viremia.

Background: Chronic inflammation persists in some people living with HIV (PLWH), even during antiretroviral therapy (ART) and is associated with premature aging. The gp120 subunit of the HIV-1 envelope glycoprotein can shed from viral and cellular membranes and can be detected in plasma and tissues, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasmatic soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, which were previously linked to CD4 depletion in vitro , could contribute to chronic inflammation, immune dysfunction, and sub-clinical cardiovascular disease in participants of the Canadian HIV and Aging cohort (CHACS) with undetectable viremia. Methods: Cross-sectional assessment of plasmatic sgp120 and anti-cluster A antibodies was performed in 386 individuals from CHACS. Their association with pro-inflammatory cytokines, as well as subclinical coronary artery disease measured by computed tomography coronary angiography was assessed using linear regression models. Results: In individuals with high levels of sgp120, anti-cluster A antibodies inversely correlated with CD4 count (p=0.042) and CD4:CD8 ratio (p=0.004). The presence of sgp120 was associated with increased plasma levels of IL-6. In participants with detectable atherosclerotic plaque and detectable sgp120, sgp120 levels, anti-cluster A antibodies and their combination correlated positively with the total volume of atherosclerotic plaques (p=0.01, 0.018 and 0.006, respectively). Conclusion: Soluble gp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of PLWH, contributing to the development of premature comorbidities. Whether drugs targeting sgp120 could mitigate HIV-associated comorbidities in PLWH with suppressed viremia warrants further studies. Key points: Soluble gp120 is detected in the plasma of people living with HIV-1 with undetectable viremia. The presence of soluble gp120 and anti-cluster A antibodies is associated with immune dysfunction, chronic inflammation, and sub-clinical cardiovascular disease.

Interpretable clinical phenotypes among patients hospitalized with COVID-19 using cluster analysis.

Background: Multiple clinical phenotypes have been proposed for coronavirus disease (COVID-19), but few have used multimodal data. Using clinical and imaging data, we aimed to identify distinct clinical phenotypes in patients admitted with COVID-19 and to assess their clinical outcomes. Our secondary objective was to demonstrate the clinical applicability of this method by developing an interpretable model for phenotype assignment. Methods: We analyzed data from 547 patients hospitalized with COVID-19 at a Canadian academic hospital. We processed the data by applying a factor analysis of mixed data (FAMD) and compared four clustering algorithms: k-means, partitioning around medoids (PAM), and divisive and agglomerative hierarchical clustering. We used imaging data and 34 clinical variables collected within the first 24 h of admission to train our algorithm. We conducted a survival analysis to compare the clinical outcomes across phenotypes. With the data split into training and validation sets (75/25 ratio), we developed a decision-tree-based model to facilitate the interpretation and assignment of the observed phenotypes. Results: Agglomerative hierarchical clustering was the most robust algorithm. We identified three clinical phenotypes: 79 patients (14%) in Cluster 1, 275 patients (50%) in Cluster 2, and 203 (37%) in Cluster 3. Cluster 2 and Cluster 3 were both characterized by a low-risk respiratory and inflammatory profile but differed in terms of demographics. Compared with Cluster 3, Cluster 2 comprised older patients with more comorbidities. Cluster 1 represented the group with the most severe clinical presentation, as inferred by the highest rate of hypoxemia and the highest radiological burden. Intensive care unit (ICU) admission and mechanical ventilation risks were the highest in Cluster 1. Using only two to four decision rules, the classification and regression tree (CART) phenotype assignment model achieved an AUC of 84% (81.5-86.5%, 95 CI) on the validation set. Conclusions: We conducted a multidimensional phenotypic analysis of adult inpatients with COVID-19 and identified three distinct phenotypes associated with different clinical outcomes. We also demonstrated the clinical usability of this approach, as phenotypes can be accurately assigned using a simple decision tree. Further research is still needed to properly incorporate these phenotypes in the management of patients with COVID-19.

Epicardial fat density, coronary artery disease and inflammation in people living with HIV.

Studies have shown an increased risk of coronary artery disease (CAD) in the human immunodeficiency virus (HIV) population. Epicardial fat (EF) quality may be linked to this increased risk. In our study, we evaluated the associations between EF density, a qualitative characteristic of fat, and inflammatory markers, cardiovascular risk factors, HIV-related parameters, and CAD. Our study was cross-sectional, nested in the Canadian HIV and Aging Cohort Study, a large prospective cohort that includes participants living with HIV (PLHIV) and healthy controls. Participants underwent cardiac computed tomography angiography to measure volume and density of EF, coronary artery calcium score, coronary plaque, and low attenuation plaque volume. Association between EF density, cardiovascular risk factors, HIV parameters, and CAD were evaluated using adjusted regression analysis. A total of 177 PLHIV and 83 healthy controls were included in this study. EF density was similar between the two groups (-77.4 ± 5.6 HU for PLHIV and -77.0 ± 5.6 HU for uninfected controls, P = .162). Multivariable models showed positive association between EF density and coronary calcium score (odds ratio, 1.07, P = .023). Among the soluble biomarkers measured in our study, adjusted analyses showed that IL2Rα, tumor necrosis factor alpha and luteizing hormone were significantly associated with EF density. Our study showed that an increase in EF density was associated with a higher coronary calcium score and with inflammatory markers in a population that includes PLHIV.

Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis.

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-32ß 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.

Anterolateral territory coronary artery bypass grafting strategies: a non-inferiority randomized clinical trial: the AMI-PONT trial.

OBJECTIVES: The main objective was to assess whether a composite coronary artery bypass grafting strategy including a saphenous vein graft bridge to distribute left internal mammary artery outflow provides non-inferior patency rates compared to conventional grafting surgery with separated left internal mammary artery to left anterior descending coronary graft and aorto-coronary saphenous vein grafts to other anterolateral targets. METHODS: All patients underwent isolated grafting surgery with cardiopulmonary bypass and received ≥2 grafts/patients on the anterolateral territory. The graft patency (i.e. non-occluded) was assessed using multislice spiral computed tomography at 1 year. RESULTS: From 2012 to 2021, 208 patients were randomized to a bridge (n = 105) or conventional grafting strategy (n = 103). Patient characteristics were comparable between groups. The anterolateral graft patency was non-inferior in the composite bridge compared to conventional grafting strategy at 1 year [risk difference 0.7% (90% confidence interval -4.8 to 6.2%)]. The graft patency to the left anterior descending coronary was no different between groups (P = 0.175). Intraoperatively, the bridge group required shorter vein length for anterolateral targets (P < 0.001) and exhibited greater Doppler flow in the mammary artery pedicle (P = 0.004). The composite outcome of death, myocardial infarction or target vessel reintervention at 30 days was no different (P = 0.164). CONCLUSIONS: Anterolateral graft patency of the composite bridge grafting strategy is non-inferior to the conventional grafting strategy at 1 year. This novel grafting strategy is safe, efficient, associated with several advantages including better mammary artery flow and shorter vein requirement, and could be a valuable alternative to conventional grafting strategies. Ten-year clinical follow-up is underway. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585285.

Assessment of Radiology Artificial Intelligence Software: A Validation and Evaluation Framework.

Artificial intelligence (AI) software in radiology is becoming increasingly prevalent and performance is improving rapidly with new applications for given use cases being developed continuously, oftentimes with development and validation occurring in parallel. Several guidelines have provided reporting standards for publications of AI-based research in medicine and radiology. Yet, there is an unmet need for recommendations on the assessment of AI software before adoption and after commercialization. As the radiology AI ecosystem continues to grow and mature, a formalization of system assessment and evaluation is paramount to ensure patient safety, relevance and support to clinical workflows, and optimal allocation of limited AI development and validation resources before broader implementation into clinical practice. To fulfil these needs, we provide a glossary for AI software types, use cases and roles within the clinical workflow; list healthcare needs, key performance indicators and required information about software prior to assessment; and lay out examples of software performance metrics per software category. This conceptual framework is intended to streamline communication with the AI software industry and provide healthcare decision makers and radiologists with tools to assess the potential use of these software. The proposed software evaluation framework lays the foundation for a radiologist-led prospective validation network of radiology AI software. Learning Points: The rapid expansion of AI applications in radiology requires standardization of AI software specification, classification, and evaluation. The Canadian Association of Radiologists' AI Tech & Apps Working Group Proposes an AI Specification document format and supports the implementation of a clinical expert evaluation process for Radiology AI software.

Association Between the Development of Subclinical Cardiovascular Disease and Human Immunodeficiency Virus (HIV) Reservoir Markers in People With HIV on Suppressive Antiretroviral Therapy.

We report that people with human immunodeficiency virus (HIV) diagnosed with coronary artery atherosclerotic plaques display higher levels of HIV DNA compared with those without atherosclerotic plaques. In a multivariable prediction model that included 27 traditional and HIV-related risk factors, measures of HIV DNA were among the most important predictors of atherosclerotic plaque formation.

A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy.

Cardiovascular disease (CVD) remains an important co-morbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed on 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 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 low HLADR high monocyte, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9 low HLADR 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.

Coronary bioresorbable stents: Non-invasive quantitative evaluation of intra- and juxta-stent plaque composition-A computed tomography longitudinal study.

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.

High frequencies of adaptive NK cells are associated with absence of coronary plaque in cytomegalovirus infected people living with HIV.

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 <4.6%, between ≥4.6% and 20% and >20%, respectively, of the total frequency of CD3-CD56dim 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.

Growth differentiation factor-15 as a biomarker of atherosclerotic coronary plaque: Value in people living with and without HIV.

Background: Increased rates of cardiovascular diseases (CVD) and larger subclinical high-risk coronary plaques in coronary CT angiography have been observed in people living with HIV (PLWH) treated with antiretroviral therapy (ART) compared to HIV-uninfected people. Growth differentiation factor-15 (GDF-15) is a cytokine emerging as an optimal marker for CVD in the general population. Methods: We cross-sectionally analyzed plasma of 95 PLWH on ART and 52 controls. We measured GDF-15, fibroblast growth factor-21 (FGF-21), glucagon-like peptide-2 (GLP-2), soluble urokinase plasminogen activator receptor (suPAR), CRP, and anti-CMV and anti-EBV IgG levels. All participants had no clinical CVD and underwent coronary CT angiography with the 3D reconstruction of coronary artery atherosclerotic plaques. Total plaque volume (TPV) and low attenuation plaque volume (LAPV, defined as density <30 Hounsfield Units) were calculated (mm3). Results: In both PLWH and controls, GDF-15 levels were increased in participants with presence of coronary plaque vs. without (p = 0.04 and p < 0.001, respectively) and correlated with TPV (r = 0.27, p = 0.009 and r = 0.62, p < 0.001, respectively) and LAPV (r = 0.28, p = 0.008, r = 0.60, p < 0.001, respectively). However, in a multivariate model, GDF-15 was independently associated with LAPV in controls only (adjusted OR 35.1, p = 0.04) and not in PLWH, mainly due to confounding by smoking. Other markers were not independently associated with plaque volume, except for anti-EBV IgGs in controls (adjusted OR 3.51, p = 0.02). Conclusion: In PLWH, GDF-15 and smoking seemed to synergistically contribute to coronary plaque volume. Conversely, increased GDF-15 levels were associated with the presence of coronary artery plaques in people without HIV, independently of CV risk factors.

Associative Prediction of Carotid Artery Plaques Based on Ultrasound Strain Imaging and Cardiovascular Risk Factors in People Living With HIV and Age-Matched Control Subjects of the CHACS Cohort.

BACKGROUND: There is a need for a specific atherosclerotic risk assessment for people living with HIV (PLWH). SETTING: A machine learning classification model was applied to PLWH and control subjects with low-to-intermediate cardiovascular risks to identify associative predictors of diagnosed carotid artery plaques. Associations with plaques were made using strain elastography in normal sections of the common carotid artery and traditional cardiovascular risk factors. METHODS: One hundred two PLWH and 84 control subjects were recruited from the prospective Canadian HIV and Aging Cohort Study (57 ± 8 years; 159 men). Plaque presence was based on clinical ultrasound scans of left and right common carotid arteries and internal carotid arteries. A classification task for identifying subjects with plaque was defined using random forest (RF) and logistic regression models. Areas under the receiver operating characteristic curves (AUC-ROCs) were applied to select 5 among 50 combinations of 4 or less features yielding the highest AUC-ROCs. RESULTS: To retrospectively classify individuals with and without plaques, the 5 most discriminant combinations of features had AUC-ROCs between 0.76 and 0.79. AUC-ROCs from RF were statistically significantly higher than those obtained with logistic regressions ( P = 0.0001). The most discriminant features of RF classifications in PLWH were age, smoking status, maximum axial strain and pulse pressure (equal weights), and sex and antiretroviral therapy exposure (equal weights). When considering the whole population, the HIV status was identified as a cofactor associated with carotid artery plaques. CONCLUSIONS: Strain elastography adds to traditional cardiovascular risk factors for identifying individuals with carotid artery plaques.

Tracking and predicting COVID-19 radiological trajectory on chest X-rays using deep learning.

Radiological findings on chest X-ray (CXR) have shown to be essential for the proper management of COVID-19 patients as the maximum severity over the course of the disease is closely linked to the outcome. As such, evaluation of future severity from current CXR would be highly desirable. We trained a repurposed deep learning algorithm on the CheXnet open dataset (224,316 chest X-ray images of 65,240 unique patients) to extract features that mapped to radiological labels. We collected CXRs of COVID-19-positive patients from an open-source dataset (COVID-19 image data collection) and from a multi-institutional local ICU dataset. The data was grouped into pairs of sequential CXRs and were categorized into three categories: 'Worse', 'Stable', or 'Improved' on the basis of radiological evolution ascertained from images and reports. Classical machine-learning algorithms were trained on the deep learning extracted features to perform immediate severity evaluation and prediction of future radiological trajectory. Receiver operating characteristic analyses and Mann-Whitney tests were performed. Deep learning predictions between "Worse" and "Improved" outcome categories and for severity stratification were significantly different for three radiological signs and one diagnostic ('Consolidation', 'Lung Lesion', 'Pleural effusion' and 'Pneumonia'; all P < 0.05). Features from the first CXR of each pair could correctly predict the outcome category between 'Worse' and 'Improved' cases with a 0.81 (0.74-0.83 95% CI) AUC in the open-access dataset and with a 0.66 (0.67-0.64 95% CI) AUC in the ICU dataset. Features extracted from the CXR could predict disease severity with a 52.3% accuracy in a 4-way classification. Severity evaluation trained on the COVID-19 image data collection had good out-of-distribution generalization when testing on the local dataset, with 81.6% of intubated ICU patients being classified as critically ill, and the predicted severity was correlated with the clinical outcome with a 0.639 AUC. CXR deep learning features show promise for classifying disease severity and trajectory. Once validated in studies incorporating clinical data and with larger sample sizes, this information may be considered to inform triage decisions.