Whole body cardiovascular magnetic resonance imaging to stratify symptomatic and asymptomatic atherosclerotic burden in patients with isolated cardiovascular disease

BACKGROUND: The aim of this study was to use whole body cardiovascular magnetic resonance imaging (WB CVMR) to assess the heart and arterial network in a single examination, so as to describe the burden of atherosclerosis and subclinical disease in participants with symptomatic single site vascular disease. METHODS: 64 patients with a history of symptomatic single site vascular disease (38 coronary artery disease (CAD), 9 cerebrovascular disease, 17 peripheral arterial disease (PAD)) underwent whole body angiogram and cardiac MR in a 3 T scanner. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cine and late gadolinium enhancement images of the left ventricle were obtained. RESULTS: Asymptomatic atherosclerotic disease with greater than 50 % stenosis in arteries other than that responsible for their presenting complain was detected in 37 % of CAD, 33 % of cerebrovascular and 47 % of PAD patients. Unrecognised myocardial infarcts were observed in 29 % of PAD patients. SAS was significantly higher in PAD patients 24 (17.5-30.5) compared to CAD 4 (2–11.25) or cerebrovascular disease patients 6 (2-10) (ANCOVA p < 0.001). Standardised atheroma score positively correlated with age (β 0.36 p = 0.002), smoking status (β 0.34 p = 0.002), and LV mass (β -0.61 p = 0.001) on multiple linear regression. CONCLUSION: WB CVMR is an effective method for the stratification of cardiovascular disease. The high prevalence of asymptomatic arterial disease, and silent myocardial infarctions, particularly in the peripheral arterial disease group, demonstrates the importance of a systematic approach to the assessment of cardiovascular disease

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Framing the discussion of microorganisms as a facet of social equity in human health

What do “microbes” have to do with social equity? These microorganisms are integral to our health, that of our natural environment, and even the “health” of the environments we build. The loss, gain, and retention of microorganisms—their flow between humans and the environment—can greatly impact our health. It is well-known that inequalities in access to perinatal care, healthy foods, quality housing, and the natural environment can create and arise from social inequality. Here, we focus on the argument that access to beneficial microorganisms is a facet of public health, and health inequality may be compounded by inequitable microbial exposure

Cohort comparison study of cardiac disease and atherosclerotic burden in type 2 diabetic adults using whole body cardiovascular magnetic resonance imaging

BACKGROUND: Whole body cardiovascular MR (WB CVMR) combines whole body angiography and cardiac MR assessment. It is accepted that there is a high disease burden in patients with diabetes, however the quantification of the whole body atheroma burden in both arterial and cardiac disease has not been previously reported. In this study we compare the quantified atheroma burden in those individuals with and without diabetes by clinical cardiovascular disease (CVD) status. METHODS: 158 participants underwent WB CVMR, and were categorised into one of four groups: (1) type 2 diabetes mellitus (T2DM) with CVD; (2) T2DM without CVD; (3) CVD without T2DM; (4) healthy controls. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cardiac MR and late gadolinium enhancement images of the left ventricle were obtained for assessment of mass, volume and myocardial scar assessment. RESULTS: 148 participants completed the study protocol—61 % male, with mean age of 64 ± 8.2 years. SAS was highest in those with cardiovascular disease without diabetes [10.1 (0–39.5)], followed by those with T2DM and CVD [4 (0–41.1)], then those with T2DM only [3.23 (0–19.4)] with healthy controls having the lowest atheroma score [2.4 (0–19.4)]. Both groups with a prior history of CVD had a higher SAS and left ventricular mass than those without (p < 0.001 for both). However after accounting for known cardiovascular risk factors, only the SAS in the group with CVD without T2DM remained significantly elevated. 6 % of the T2DM group had evidence of silent myocardial infarct, with this subcohort having a higher SAS than the remainder of the T2DM group [7.7 (4–19) vs. 2.8 (0–17), p = 0.024]. CONCLUSIONS: Global atheroma burden was significantly higher in those with known cardiovascular disease and without diabetes but not in those with diabetes and cardiovascular disease suggesting that cardiovascular events may occur at a lower atheroma burden in diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0284-2) contains supplementary material, which is available to authorized users

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Adoption of high-sensitivity cardiac troponin for risk stratification of patients with suspected myocardial infarction: a multicentre cohort study

Background: Guidelines recommend high-sensitivity cardiac troponin to risk stratify patients with possible myocardial infarction and identify those eligible for discharge. Our aim was to evaluate adoption of this approach in practice and to determine whether effectiveness and safety varies by age, sex, ethnicity, or socioeconomic deprivation status. Methods: A multi-centre cohort study was conducted in 13 hospitals across the United Kingdom from November 1st, 2021, to October 31st, 2022. Routinely collected data including high-sensitivity cardiac troponin I or T measurements were linked to outcomes. The primary effectiveness and safety outcomes were the proportion discharged from the Emergency Department, and the proportion dead or with a subsequent myocardial infarction at 30 days, respectively. Patients were stratified using peak troponin concentration as low (sex-specific 99th percentile). Findings: In total 137,881 patients (49% [67,709/137,881] female) were included of whom 60,707 (44%), 42,727 (31%), and 34,447 (25%) were stratified as low-, intermediate- and high-risk, respectively. Overall, 65.8% (39,918/60,707) of low-risk patients were discharged from the Emergency Department, but this varied from 26.8% [2200/8216] to 93.5% [918/982] by site. The safety outcome occurred in 0.5% (277/60,707) and 11.4% (3917/34,447) of patients classified as low- or high-risk, of whom 0.03% (18/60,707) and 1% (304/34,447) had a subsequent myocardial infarction at 30 days, respectively. A similar proportion of male and female patients were discharged (52% [36,838/70,759] versus 54% [36,113/67,109]), but discharge was more likely if patients were <70 years old (61% [58,533/95,227] versus 34% [14,428/42,654]), from areas of low socioeconomic deprivation (48% [6697/14,087] versus 43% [12,090/28,116]) or were black or asian compared to caucasian (62% [5458/8877] and 55% [10,026/18,231] versus 46% [35,138/75,820]). Interpretation: Despite high-sensitivity cardiac troponin correctly identifying half of all patients with possible myocardial infarction as being at low risk, only two-thirds of these patients were discharged. Substantial variation in the discharge of patients by age, ethnicity, socioeconomic deprivation, and site was observed identifying important opportunities to improve care. Funding: UK Research and Innovation

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies