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.

Oncogenic gain of function due to p53 amyloids occurs through aberrant alteration of cell cycle and proliferation.

Transcription factor p53 (also known as TP53) has been shown to aggregate into cytoplasmic and nuclear inclusions, compromising its native tumor suppressive functions. Recently, p53 has been shown to form amyloids, which play a role in conferring cancerous properties to cells, leading to tumorigenesis. However, the exact pathways involved in p53 amyloid-mediated cellular transformations are unknown. Here, using an in cellulo model of full-length p53 amyloid formation, we demonstrate the mechanism of loss of p53 tumor-suppressive function with concomitant oncogenic gain of functions. Global gene expression profiling of cells suggests that p53 amyloid formation dysregulates genes associated with the cell cycle, proliferation, apoptosis and senescence along with major signaling pathways. This is further supported by a proteome analysis, showing a significant alteration in levels of p53 target proteins and enhanced metabolism, which enables the survival of cells. Our data indicate that specifically targeting the key molecules in pathways affected by p53 amyloid formation, such as cyclin-dependent kinase-1, leads to loss of the oncogenic phenotype and induces apoptosis of cells. Overall, our work establishes the mechanism of the transformation of cells due to p53 amyloids leading to cancer pathogenesis. This article has an associated First Person interview with the first author of the paper.

A Review on Emerging Techniques for Diagnosis of Colorectal Cancer.

Common detection methods in practice for diagnosing colorectal cancer (CRC) are painful and invasive leading to less participation of individuals for CRC diagnosis. Whereas, improved or enhanced imaging systems and other minimally invasive techniques with shorter detection times deliver greater detail and less discomfort in individuals. Thus, this review is a summary of the diagnostic tests, ranging from the simple potential use in developing a flexible CRC treatment to the patient's potential benefits in receiving less invasive procedures and the advanced treatments that might provide a better assessment for the diagnosis of CRC and reduce the mortality related to CRC.

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.

Epigenetic perspectives associated with COVID-19 infection and related cytokine storm: an updated review.

PURPOSE: The COVID-19 pandemic caused by the novel Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has put the world in a medical crisis for the past three years; nearly 6.3 million lives have been diminished due to the virus outbreak. This review aims to update the recent findings on COVID-19 infections from an epigenetic scenario and develop future perspectives of epi-drugs to treat the disease. METHODS: Original research articles and review studies related to COVID-19 were searched and analyzed from the Google Scholar/PubMed/Medline databases mainly between 2019 and 2022 to brief the recent work. RESULTS: Numerous in-depth studies of the mechanisms used by SARS-CoV-2 have been going on to minimize the consequences of the viral outburst. Angiotensin-Converting Enzyme 2 receptors and Transmembrane serine protease 2 facilitate viral entry to the host cells. Upon internalization, it uses the host machinery to replicate viral copies and alter the downstream regulation of the normal cells, causing infection-related morbidities and mortalities. In addition, several epigenetic regulations such as DNA methylation, acetylation, histone modifications, microRNA, and other factors (age, sex, etc.) are responsible for the regulations of viral entry, its immune evasion, and cytokine responses also play a major modulatory role in COVID-19 severity, which has been discussed in detail in this review. CONCLUSION: Findings of epigenetic regulation of viral pathogenicity open a new window for epi-drugs as a possible therapeutical approach against COVID-19.

Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus.

OBJECTIVES: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE. METHODS: Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed. RESULTS: Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose. CONCLUSION: PGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE. TRIAL REGISTRATION NUMBER: NCT02338999.

Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells.

Enrichment of angiomotin (AMOT) in the ectoplacental cone of E7.5 murine placenta prompted our investigation on the role of AMOT in trophoblast differentiation. We show here that AMOT levels increased in mouse placenta during gestation and also upon induction of differentiation in trophoblast stem cell ex vivo. Proteomic data unravelling AMOT-interactome in trophoblast cells indicated a majority of AMOT interactors to be involved in protein translation. In-depth analysis of AMOT-interactome led to identification of eukaryotic translation initiation factor 4A (eIF4A) as the most plausible AMOT interactor. Loss of function of AMOT enhanced, whereas, gain in function resulted in decline of global protein synthesis in trophoblast cells. Bioinformatics analysis evaluating the potential energy of AMOT-eIF4A binding suggested a strong AMOT-eIF4A interaction using a distinct groove encompassing amino acid residue positions 238 to 255 of AMOT. Co-immunoprecipitation of AMOT with eIF4A reaffirmed AMOT-eIF4A association in trophoblast cells. Deletion of 238 to 255 amino acids of AMOT resulted in abrogation of AMOT-eIF4A interaction. In addition, 238 to 255 amino acid deletion of AMOT was ineffective in eliciting AMOT's function in reducing global protein synthesis. Interestingly, AMOT-dependent sequestration of eIF4A dampened its loading to the m7 -GTP cap and hindered its interaction with eIF4G. Furthermore, enhanced AMOT expression in placenta was associated with intrauterine growth restriction in both rats and humans. These results not only highlight a hitherto unknown novel function of AMOT in trophoblast cells but also have broad biological implications as AMOT might be an inbuilt switch to check protein synthesis in developmentally indispensable trophoblast cells.

Five Years of Sacubitril/Valsartan-a Safety Analysis of Randomized Clinical Trials and Real-World Pharmacovigilance.

PURPOSE: In PARADIGM-HF, sacubitril/valsartan showed a significant reduction in mortality and hospitalization for patients with heart failure with reduced ejection fraction. Despite proven efficacy, sacubitril/valsartan has moderate uptake in clinical practice. This study explores the safety profile of sacubitril/valsartan by comparing adverse events in RCT and real-world use. METHODS: We studied hypotension, renal dysfunction, hyperkalemia, and angioedema associated with sacubitril/valsartan in RCTs and pharmacovigilance databases. A random-effects meta-analysis was performed with six RCTs investigating sacubitril/valsartan vs. control/comparators in heart failure patients. WHO's VigiBase, FAERS, and EMA's EudraVigilance were mined to obtain spontaneously reported real-world adverse events. Disproportionality analysis was performed with the FDA's OpenVigil 2.0. RESULTS: Six RCTs enrolled 15,538 patients with heart failure with reduced and preserved ejection fractions. There was no statistical difference for the composite of hypotension, renal dysfunction, hyperkalemia, and angioedema between sacubitril/valsartan and its comparators viz. ACEi or ARBs (OR 1.23, CI 0.98-1.56; p = 0.08). A total of 103,038 adverse events were registered in the spontaneous reporting systems. Hypotension was the most reported adverse event. Proportions of composite adverse events were 20% in VigiBase, 17% in FAERS, and 39% with EudraVigilance. Disproportionality analysis showed a lower risk of adverse events with sacubitril/valsartan than other guideline-directed heart failure medications used in clinical practice. CONCLUSION: With increased uptake of sacubitril/valsartan, risks of hypotension, renal dysfunction, hyperkalemia, and angioedema appear low and acceptable in RCTs and global clinical practice.

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.

Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus.

Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE is characterized by elevated levels of a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, and pathogenic heterogeneity of LDGs remain to be systematically determined. Transcriptomics and epigenetic assessment of lupus LDGs, autologous normal-density neutrophils, and healthy control neutrophils was performed by bulk and single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. Functional readouts were compared among neutrophil subsets. SLE LDGs display significant transcriptional and epigenetic heterogeneity and comprise 2 subpopulations of intermediate-mature and immature neutrophils, with different degrees of chromatin accessibility and differences in transcription factor motif analysis. Differences in neutrophil extracellular trap (NET) formation, oxidized mitochondrial DNA release, chemotaxis, phagocytosis, degranulation, ability to harm the endothelium, and responses to type I interferon (IFN) stimulation are evident among LDG subsets. Compared with other immune cell subsets, LDGs display the highest expression of IFN-inducible genes. Distinct LDG subsets correlate with specific clinical features of lupus and with the presence and severity of coronary artery disease. Phenotypic, functional, and pathogenic neutrophil heterogeneity are prevalent in SLE and may promote immune dysregulation and prominent vascular damage characteristic of this disease.

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.

Dynamic Alteration in the Vaginal Secretory Proteome across the Early and Mid-Trimesters of Pregnancy.

Pregnancy is characterized by intense physiological and structural alterations in the vagina, cervix, and overlying fetal membranes. High vaginal fluid (HVF) is a proximal fluid that covers the lower part of the female reproductive system and the severity of vaginal pathology often adversely affects pregnancy outcomes. To identify the correlation of vaginal fluid proteome dynamics and physiological changes during the progression of pregnancy, a longitudinal study was performed on 20 pregnant women who delivered a baby in >37 weeks without any complications. SWATH-MS-based label-free quantitative proteomics was performed to profile the HVF proteome at three time points defined as V1 (7-12 weeks), V2 (18-20 weeks), and V3 (26-28 weeks). Linear mixed-effect models were used to estimate protein abundance as a function of the period of gestational age. In this study, we identified 1015 HVF proteins and 61 of them were significantly altered until late second trimester. Our result demonstrates that the HVF proteins reveal gestational age-specific expression patterns and the function of these proteins is associated with tissue remodeling, organ development, and microbial defense. Our study provides an opportunity to monitor the underlying physiology of pregnancy that may be further probed for the biomarker identification in pregnancy-related adverse outcomes. Data are available via ProteomeXchange with identifiers PXD014846 and PXD021811.

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.

The application of molecular imaging to advance translational research in chronic inflammation.

Over the past several decades, molecular imaging techniques to assess cellular processes in vivo have been integral in advancing our understanding of disease pathogenesis. 18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) imaging in particular has shaped the field of atherosclerosis research by highlighting the importance of underlying inflammatory processes that are responsible for driving disease progression. The ability to assess physiology using molecular imaging, combining it with anatomic delineation using cardiac coronary angiography (CCTA) and magnetic resonance imaging (MRI) and lab-based techniques, provides a powerful combination to advance both research and ultimately clinical care. In this review, we demonstrate how molecular imaging studies, specifically using 18-FDG PET, have revealed that early vascular disease is a systemic process with multiple, concurrent biological mechanisms using inflammatory diseases as a basis to understand early atherosclerotic mechanisms in humans.

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.