SenNet recommendations for detecting senescent cells in different tissues.

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.

Identification and functional analysis of senescent cells in the cardiovascular system using omics approaches.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, and senescent cells have emerged as key contributors to its pathogenesis. Senescent cells exhibit cell cycle arrest and secrete a range of proinflammatory factors, termed the senescence-associated secretory phenotype (SASP), which promotes tissue dysfunction and exacerbates CVD progression. Omics technologies, specifically transcriptomics and proteomics, offer powerful tools to uncover and define the molecular signatures of senescent cells in cardiovascular tissue. By analyzing the comprehensive molecular profiles of senescent cells, omics approaches can identify specific genetic alterations, gene expression patterns, protein abundances, and metabolite levels associated with senescence in CVD. These omics-based discoveries provide insights into the mechanisms underlying senescence-induced cardiovascular damage, facilitating the development of novel diagnostic biomarkers and therapeutic targets. Furthermore, integration of multiple omics data sets enables a systems-level understanding of senescence in CVD, paving the way for precision medicine approaches to prevent or treat cardiovascular aging and its associated complications.

Length of stay and cost of care associated with admissions for atrial fibrillation among patients with cancer.

BACKGROUND: The aim of this study is to assess the burden of AF-related hospitalizations inclusive of inflation-adjusted cost-of-care and length-of-stay (LOS) among cancer patients and the impact of direct current cardioversion (DCCV) on these outcomes. METHODS: Using the National Inpatient Sample (NIS), patients hospitalized with either a primary or secondary diagnosis of AF and comorbid cancer were identified and both cost of hospitalization and LOS were evaluated for each group. Subgroup analyses were performed for specific cancer types (breast, lung, colon, prostate and lymphoma), and those receiving DCCV. RESULTS: The prevalence of co-morbid AF was 8.2 million (16%) and 35.5 million (10%) among those with vs. those without cancer, respectively (odds ratio = 1.6, 95% confidence interval = 1.5-1.7; P < 0.001). Over time, both primary and prevalent AF admissions among those with comorbid cancer increased from 1.1% and 12.3% in 2003 to 1.5% and 21% in 2015, respectively. The total cost of hospitalization increased 94.4% among those with AF and comorbid cancer compared to 23.9% among those without cancer. Among the subgroup of patients with comorbid cancer and primary admission for AF undergoing DCCV, length of stay (2.7 vs. 2.2 days; P < 0.001, model 1) and cost of care ($7,093 vs. 6,152; P < 0.001) were both significantly higher. CONCLUSIONS: AF related admissions are increasing for all populations especially amongst those patients with a comorbid diagnosis of cancer, including all cancer subtypes evaluated. Among those patients who underwent DCCV, cancer patients had longer length of stay and increased health care costs.

The neutrophil-lymphocyte ratio and incident atherosclerotic events: analyses from five contemporary randomized trials.

AIMS: The neutrophil-lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapy. METHODS AND RESULTS: Baseline and on-treatment NLRs were calculated from complete blood counts among 60 087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14-25%, P < 0.0001], 31% in SPIRE-1 (95% CI 14-49%, P = 0.00007), 27% in SPIRE-2 (95% CI 12-43%, P = 0.0002), 9% in CIRT (95% CI 0.2-20%, P = 0.045), and 11% in JUPITER (95% CI 1-22%, P = 0.03). While lipid-lowering agents had no significant impact on the NLR, anti-inflammatory therapy with canakinumab lowered the NLR (P < 0.0001). CONCLUSION: The NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1ß blockade with canakinumab.

Etiology and pathophysiology of heart failure in people with HIV.

HIV-associated cardiomyopathy is a well-established sequela in people infected with HIV (PHIV). Despite significant advances in HIV management through the use of highly active anti-retroviral therapy (HAART), PHIV on HAART continue to have elevated risk of cardiomyopathy and heart failure, even when accounting for known cardiovascular risk factors. This review article will explore the proposed mechanisms by which chronic HIV infection induces cardiomyopathy and heart failure in the setting of HAART. Evaluation, work-up, and management of cardiomyopathy in PHIV will also be briefly discussed. The advent of HAART has altered the pathophysiology HIV-associated cardiomyopathy from a rapidly progressive cardiomyopathy, often with pericardial involvement, into a chronic process involving inflammation and persistent immune dysregulation. With the significant decrease in AIDS-related deaths, the prevalence of cardiomyopathy and the mortality associated with heart failure in PHIV have increased. Multiple immune-related and inflammatory mechanisms have been proposed, which may provide insight into evaluation and management of cardiomyopathy in PHIV.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

Neighborhood environment perceptions associate with depression levels and cardiovascular risk among middle-aged and older adults: Data from the Washington, DC cardiovascular health and needs assessment.

OBJECTIVES: Little is understood about associations between neighborhood characteristics and depression, a cardiovascular disease (CVD) risk factor, in diverse populations. We examined relationships between perceived/objective neighborhood characteristics, depression, and CVD markers within the Washington, DC CV Health/Needs Assessment, an evaluation among predominantly African-American (AA) adults in resource-limited DC communities. METHOD: Factor analysis of overall neighborhood environment perception (NEP) identified three NEP sub-scores:1) violence; 2) physical/social environment; 3) social cohesion (higher score = more favorable perception). Objective neighborhood characteristics were measured by geospatially-derived scores of walkability, transportation, and crime. Depression was defined by the revised Center for Epidemiologic Studies Depression Scale (CESD-R). We used linear-regression modeling to examine neighborhood measures and CESD-R associations. To investigate a subsequent connection with CVD risk, we examined relationships between CESD-R and CVD-associated cytokines in a population subset. RESULTS: Participants (N = 99; mean age = 59.06; 99% AA) had a mean CESD-R score = 5.8(SD = 8.88). In adjusted models, CESD-R scores decreased by 0.20 units (p = 0.01) for every overall NEP unit-increase. Perceived physical/social environment (ß = -0.34, p = 0.04) and social cohesion (ß = -0.82, p = 0.01) were related to CESD-R while perceived violence was not (ß = -0.28, p = 0.1). Of objective neighborhood environment measures (i.e. walk, transit, bike, personal crime, and property crime scores), only property crime score was associated with depression (ß = 4.99, p < 0.03). In population subset (n = 42), higher CESD-R associated with higher IL-1ß (ß = 21.25, p < 0.01) and IL-18 (ß = 0.006, p = 0.01). CONCLUSION: Favorable neighborhood perceptions are related to lower depressive symptoms in a predominantly AA cohort from Washington, DC resource-limited communities. Neighborhood perceptions appear to be strongly associated with depressive symptoms compared to objective characteristics. Increasing CESD-R scores were related to higher pro-inflammatory markers. Improving neighborhood perceptions may be beneficial to psychological well-being and CV health for urban minority residents.

Periodontal Inflammation and the Risk of Cardiovascular Disease.

PURPOSE OF REVIEW: The role of oral bacteremia and periodontal inflammation driving atherosclerosis is still under investigation. This review article highlights the role of periodontal inflammation and oral microorganisms in the development and progression of atherosclerosis and cardiovascular diseases. RECENT FINDINGS: Association between periodontal and cardiovascular diseases has been well characterized, but causal correlation is yet to be established. For instance, untreated gingivitis can progress to periodontitis. Periodontal disease has been associated with several systemic diseases one of which is atherosclerosis. One possible association that was documented in literature is that poor oral hygiene leads to bacteremia, which in turn can cause bacterial growth over atherosclerotic coronary artery plaques and possibly worsen coronary artery disease. It is crucial that clinicians understand the association between periodontal and cardiovascular disease. A comprehensive treatment for periodontitis and re-establishment of a healthy periodontium can help in reduction of overall inflammation in the body. This may play an important role in prevention of cardiovascular disease, though future research is needed to establish this.

Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis.

RATIONALE: Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis. OBJECTIVE: To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis. METHODS AND RESULTS: Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased body mass index, and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL; P <0.05 for all) with significant association of oxidized LDL (ß=0.10; P=0.020) and oxHDL (ß=-0.11; P=0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82; P=0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03; P<0.001) and with a concomitant decrease in NCB at 1 year (1.04±0.44 versus 0.95±0.32; P=0.03). CONCLUSIONS: Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.

Application of machine learning to determine top predictors of noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with elevated risk of heart attack and increased accumulation of subclinical noncalcified coronary burden by coronary computed tomography angiography (CCTA). Machine learning algorithms have been shown to effectively analyze well-characterized data sets. OBJECTIVE: In this study, we used machine learning algorithms to determine the top predictors of noncalcified coronary burden by CCTA in psoriasis. METHODS: The analysis included 263 consecutive patients with 63 available variables from the Psoriasis Atherosclerosis Cardiometabolic Initiative. The random forest algorithm was used to determine the top predictors of noncalcified coronary burden by CCTA. We evaluated our results using linear regression models. RESULTS: Using the random forest algorithm, we found that the top 10 predictors of noncalcified coronary burden were body mass index, visceral adiposity, total adiposity, apolipoprotein A1, high-density lipoprotein, erythrocyte sedimentation rate, subcutaneous adiposity, small low-density lipoprotein particle, cholesterol efflux capacity and the absolute granulocyte count. Linear regression of noncalcified coronary burden yielded results consistent with our machine learning output. LIMITATION: We were unable to provide external validation and did not study cardiovascular events. CONCLUSION: Machine learning methods identified the top predictors of noncalcified coronary burden in psoriasis. These factors were related to obesity, dyslipidemia, and inflammation, showing that these are important targets when treating comorbidities in psoriasis.

Readmission after inferior vena cava filter placement for acute venous thromboembolism in the United States: Impact of a cancer diagnosis.

BACKGROUND: Inferior vena cava filter (IVCF) use is common after a venous thromboembolic event (VTE). Cancer is associated with higher rates of VTEs and is also seen in a significant proportion of patients requiring IVCF. As hospital readmissions remain a frequently scrutinized metric, we sought to evaluate the impact of cancer on hospital-readmission rates and in-hospital outcomes among patients with VTEs who received an IVCF. METHODS: Leveraging the 2013 to 2014 Nationwide Readmission Database, we identified adult patients presenting with a VTE in the United States and evaluated 30-day readmission rates and readmission in-hospital outcomes postindex-admission. Multivariable logistic regression was used to identify factors associated with readmission after an index-procedure, including traditional and nontraditional cardiovascular risk factors, as well as hospital-level characteristics. RESULTS: Among the 619 241 patients presenting with a VTE at index-admission, 11.2% of patients received IVCF on index-admission, of which 30.9% had cancer. The 30-day readmission rate amongst IVCF recipients was 15.8% (N = 10 927), and 19.9% amongst those with cancer compared to 13.9% in patients without cancer (P < .001). Moreover, cancer patients had longer lengths of stay in the hospital (4.5 ± 0.2 vs 4.0 ± 0.1 days; P = .02), higher cost of care ($10 900 ± 308 vs $9242 ± 206; P = .007), but no difference in mortality (8.3% vs 6.3%; P = .70) during readmission compared to noncancer patients. CONCLUSION: Readmission after IVCF placement is common. In patients readmitted after an IVCF implantation, those with cancer have longer hospital stays and higher costs of care. However, in-hospital mortality is similar to those without cancer.

The effect of catheter-directed thrombolytic use on readmission rates and in-hospital outcomes among cancer patients with venous thromboembolism in the United States.

BACKGROUND: Cancer inducing a hypercoagulable state, venous thromboembolism (VTE) remains a leading cause of morbidity and mortality globally. We assessed the impacts of cancer on the likelihood for readmission after a VTE-targeted procedure. METHODS: We created a new cohort using discharge-level data from all hospitalizations from State Inpatient Databases of geographically dispersed participating states (18-27 states). RESULTS: In those presenting with VTE during index-admission (619 241), 2.4% patients underwent catheter directed thrombolytic therapy (CDL) on index admission and among those 20.3% had cancer. Moreover, the 30-day readmission rate amongst CDL recipients (10 776 overall) was 14.3% in those with cancer compared to 8.8% in those with no cancer history (P < .0001). Additionally, in-hospital mortality (5.7% vs 1.1%; P = 0.009) and cost-of-care ($11 014 ± 914 vs $10 520 ± 534; P = .04) was significantly higher in cancer compared to noncancer. CONCLUSION: The use of CDL does not appear to reduce the risk of returning for a VTE-related admission in cancer.

Association of aortic vascular uptake of 18FDG by PET/CT and aortic wall thickness by MRI in psoriasis: a prospective observational study.

BACKGROUND: The contribution of inflammation to the incidence of cardiovascular disease (CVD) has been increasingly recognized in recent years. We investigated the relationship of aortic vascular uptake of 18F-FDG by PET/CT and aortic wall thickness (AWT) by MRI in psoriasis, a chronic inflammatory disease with increased incidence of CVD. One hundred sixty-five patients with plaque psoriasis participated in an ongoing longitudinal cohort study. Subclinical atherosclerosis was assessed as aortic uptake of 18F-FDG by PET/CT reported as target-to-background ratio (TBR) and AWT by MRI reported as maximal thickness. RESULTS: Patients with psoriasis were middle aged, predominantly male, and had mild CV risk by traditional risk factors. Psoriasis severity as measured by PASI score was a notable determinant of AWT (ρ = 0.20, p = 0.01). Moreover, aortic vascular uptake of 18F-FDG associated with AWT by MRI at baseline in unadjusted analysis (ß = 0.27 p = 0.001) and following adjustment for traditional cardiovascular risk factors, waist-to-hip ratio, and statin use (ß = 0.21 p = 0.01). Finally, following 1 year of psoriasis treatment, a decrease in aortic vascular uptake of 18F-FDG was associated with a reduction in AWT in fully adjusted models (ß = 0.33, p = 0.02). CONCLUSION: In conclusion, we demonstrate that psoriasis severity and aortic vascular uptake of 18F-FDG in the aorta were associated with AWT. Following treatment of psoriasis, a decrease in aortic vascular uptake of 18F-FDG was associated with a reduction in AWT at 1 year. These findings suggest that aortic vascular uptake of 18F-FDG is associated with early evidence of vascular disease assessed by aortic wall thickness. Prospective studies in larger populations including other inflammatory diseases are warranted.

Application of Non-invasive Imaging in Inflammatory Disease Conditions to Evaluate Subclinical Coronary Artery Disease.

PURPOSE OF REVIEW: Traditional risk models, such as the Framingham risk score, fail to capture the increased cardiovascular disease risk seen in patients with chronic inflammatory diseases. This review will cover imaging modalities and their emerging applications in assessing subclinical cardiovascular disease for both research and clinical care in patients with chronic inflammatory diseases. RECENT FINDINGS: Multiple imaging modalities have been studied to assess for subclinical cardiovascular disease via functional/physiologic, inflammatory, and anatomic assessment in patients with chronic inflammatory diseases. The use of imaging to evaluate subclinical cardiovascular disease in patients with chronic inflammatory diseases has the potential to capture early sub-clinical atherosclerosis, to improve risk stratification of future cardiovascular events, and to guide effective disease management.

Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study.

BACKGROUND: Psoriasis, a chronic inflammatory disease associated with an accelerated risk of myocardial infarction, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease burden composed of noncalcified plaques with high-risk features. However, inadequate efforts have been made to directly measure coronary artery disease in this vulnerable population. As such, we sought to compare total coronary plaque burden and noncalcified coronary plaque burden (NCB) and high-risk plaque (HRP) prevalence between patients with psoriasis (n=105), patients with hyperlipidemia eligible for statin therapy under National Cholesterol Education Program-Adult Treatment Panel III guidelines (n=100) who were ≈10 years older, and healthy volunteers without psoriasis (n=25). METHODS: Patients underwent coronary computed-tomography angiography for total coronary plaque burden and NCB quantification and HRP identification, defined as low attenuation (<30 hounsfield units), positive remodeling (>1.10), and spotty calcification. A consecutive sample of the first 50 patients with psoriasis was scanned again 1 year after therapy. RESULTS: Despite being younger and at lower traditional risk than patients with hyperlipidemia, patients with psoriasis had increased NCB (mean±SD: 1.18±0.33 versus 1.11±0.32, P=0.02) and similar HRP prevalence (P=0.58). Furthermore, compared to healthy volunteers, patients with psoriasis had increased total coronary plaque burden (1.22±0.31 versus 1.04±0.22, P=0.001), NCB (1.18±0.33 versus 1.03±0.21, P=0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1-31.7; P=0.03). Last, among patients with psoriasis followed for 1 year, improvement in psoriasis severity was associated with improvement in total coronary plaque burden (ß=0.45, 0.23-0.67; P<0.001) and NCB (ß=0.53, 0.32-0.74; P<0.001) beyond traditional risk factors. CONCLUSIONS: Patients with psoriasis had greater NCB and increased HRP prevalence than healthy volunteers. In addition, patients with psoriasis had elevated NCB and equivalent HRP prevalence as older patients with hyperlipidemia. Last, modulation of target organ inflammation (eg, skin) was associated with an improvement in NCB at 1 year, suggesting that control of remote sites of inflammation may translate into reduced coronary artery disease risk.

Low cholesterol efflux capacity and abnormal lipoprotein particles in youth with type 1 diabetes: a case control study.

BACKGROUND: Patients with type 1 diabetes (T1DM) have increased mortality from cardiovascular disease (CVD). Risk factors for CVD include an elevation of LDL (LDLp) and small HDL (sHDLp) particles, and a decrease in reverse cholesterol transport i.e. HDL-cholesterol efflux capacity (CEC). Our objective was to compare lipoprotein particles and CEC between T1DM and healthy controls (HC) and to explore the associations between NMR lipid particles and cholesterol efflux. METHODS: 78 patients with T1DM and 59 HC underwent fasting lipoprotein profile testing by NMR and measurements of CEC by cell-based method. The associations between NMR lipid particles with CEC were analyzed using multivariable linear regression models. RESULTS: Youth with T1DM had higher total LDLp 724 [(563-985) vs 622 (476-794) nmol/L (P = 0.011)] (Maahs et al. in Circulation 130(17):1532-58, 2014; Shah et al. in Pediatr Diabetes 16(5):367-74, 2015), sHDLp [11.20 (5.7-15.3) vs 7.0 (3.2-13.1) µmol/L (P = 0.021)], and lower medium HDLp [11.20 (8.5-14.5) vs 12.3 (9-19.4), (P = 0.049)] and lower CEC (0.98 ± 0.11% vs 1.05 ± 0.15%, P = 0.003) compared to HC. Moreover, CEC correlated with sHDLp (ß = - 0.28, P = 0.045) and large HDLp (ß = 0.46, P < 0.001) independent of age, sex, ethnicity, BMIz, HbA1c, hsCRP and total HDLp in the diabetic cohort. CONCLUSIONS: Youth with T1DM demonstrated a more atherogenic profile including higher sHDL and LDLp and lower CEC. Future efforts should focus on considering adding lipoprotein particles and CEC in CVD risk stratification of youth with T1DM. Trial registration Clinical Trials Registration Number NCT02275091.

Branchial cleft cysts: a pictorial review.

Cystic masses of the neck may represent a wide variety of pathological conditions. Among these, branchial anomalies are the commonest paediatric congenital lesions of the head and neck. This article intends to review this condition under the same headings, as well as facilitate their diagnosis with the help of appropriate radiological findings of patients diagnosed with these anomalies. In order to make an accurate diagnosis, it is imperative to have an idea about the possible differentials, and the normal embryological development of the branchial arches, as well as their anomalies, in the form of sinuses, fistulae, and cysts, with their features and subtypes. The medical history of the patient and clinical manifestations helps in suspecting branchial cleft cysts; confirmatory imaging modalities include computed tomography, magnetic resonance imaging, ultrasonography, and fine-needle aspiration. The mainstay of management is usually by surgical excision. The location, clinical picture, and radiological correlation, along with a strong degree of suspicion for the condition, facilitates the diagnosis of this relatively common embryological anomaly.

Psoriasis as a human model of disease to study inflammatory atherogenesis.

Inflammation is known to play a significant role in the process of atherogenesis and cardiovascular disease (CVD). Indeed, patients with chronic inflammatory diseases are at increased risk for cardiovascular events. However, the mechanisms linking chronic inflammation and CVD remain poorly understood. Psoriasis, a chronic inflammatory skin disease associated with a greater risk of early cardiovascular events, provides a suitable human model to study the pathophysiology of inflammatory atherogenesis in humans. Additionally, cytokines such as TNF-α, IL-17A, and other immune pathways are the common links between the pathogenesis of psoriasis and atherosclerosis, and hence the approved treatments for psoriasis, which include selective cytokine inhibition (e.g., anti-TNF, anti-IL-17A, and anti-IL-12/23) and immune modulation (e.g., methotrexate or cyclosporine), provide an opportunity to examine the effect of modulating these pathways on atherogenesis. We have been using this human model in a large, prospective cohort study, and this review summarizes our approach and results of using this human model to study inflammatory atherogenesis. Specifically, we review simultaneous multimodal imaging of several vascular beds using 18fludeoxyglucose positron emission tomography/computed tomography, 18fludeoxyglucose positron emission tomography/MRI, and coronary computed tomography angiography as well as cardiovascular biomarkers to better understand how modulation of inflammation may impact vascular diseases.