Massive pericardial hematoma simulating constrictive pericarditis: a complication of radiofrequency catheter ablation

AbstractJ Thorac Cardiovasc Surg 1998;115:726-

Isotopic and geologic studies to identify the sources of sulfate in groundwater containing high barium concentrations

"Final report, project no. A-100-I11.""November 1981"--P. 1 of cover.Bibliography: p. 36-39."UILU-WRC-81-0165"--P. 1 of cover

Stroke Severity Predicted by Aortic Atheroma Detected by Ultra-Fast and Cardiac-Gated Chest Tomography†

Background and Purpose: The presence of aortic atherosclerosis is an independent risk factor for secondary stroke. The present study was designed to have an initial exploration of the correlation between the load and extent of aortic atheroma (AA) and initial stroke severity or clinical outcome 3 months after stroke. Methods: Cardiac-gated chest tomography (CGCT) was used to detect and measure AA in patients with acute ischemic stroke as shown by our group in prior prospective studies and this is part four sub-exploratory study of the same cohort. The National Institute of Health Stroke Scale (NIHSS) was used to assess the initial stroke severity, and the modified Rankin Scale (mRS) was used to assess 3-month outcome. Results: Thirty-two patients underwent CGCT for evaluation of AA, and 21 were found to have AA. AA was more prevalent in patient with NIHSS >6 (14/17 versus 7/15, p-value 0.03). Applying the multiple logistic regression and propensity score adjustment (using the propensity of having AA given the baseline features as covariates) showed a non-significant trend that AA is three times more likely to be associated with NIHSS >6 (p = 0.08, OR 3.08, 95% CI 0.94–13.52). There was no evidence of association of AA with 3-month functional outcome (mRS): 11/14 (78.6%) mRS >1 had AA, and 10/18 (55.5%) of those with mRS ≤1 had AA (p = 0.27). Conclusion: In our current study with limited sample number and exploratory nature, the presence of AA on CGCT with acute ischemic stroke patients may be associated with worse neurological deficit at presentation. There was no evidence of association with 3-month functional outcome using the mRS

Evaluation of left ventricular ejection fraction using through-time radial GRAPPA

BACKGROUND: The determination of left ventricular ejection fraction using cardiovascular magnetic resonance (CMR) requires a steady cardiac rhythm for electrocardiogram (ECG) gating and multiple breathholds to minimize respiratory motion artifacts, which often leads to scan times of several minutes. The need for gating and breathholding can be eliminated by employing real-time CMR methods such as through-time radial GRAPPA. The aim of this study is to compare left ventricular cardiac functional parameters obtained using current gold-standard breathhold ECG-gated functional scans with non-gated free-breathing real-time imaging using radial GRAPPA, and to determine whether scan time or the occurrence of artifacts are reduced when using this real-time approach. METHODS: 63 patients were scanned on a 1.5T CMR scanner using both the standard cardiac functional examination with gating and breathholding and the real-time method. Total scan durations were noted. Through-time radial GRAPPA was employed to reconstruct images from the highly accelerated real-time data. The blood volume in the left ventricle was assessed to determine the end systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) for both methods, and images were rated for the presence of artifacts and quality of specific image features by two cardiac readers. Linear regression analysis, Bland-Altman plots and two-sided t-tests were performed to compare the quantitative parameters. A two-sample t-test was performed to compare the scan durations, and a two-sample test of proportion was used to analyze the presence of artifacts. For the reviewers´ ratings the Wilcoxon test for the equality of the scores’ distributions was employed. RESULTS: The differences in EF, EDV, and ESV between the gold-standard and real-time methods were not statistically significant (p-values of 0.77, 0.82, and 0.97, respectively). Additionally, the scan time was significantly shorter for the real-time data collection (p<0.001) and fewer artifacts were reported in the real-time images (p<0.01). In the qualitative image analysis, reviewers marginally preferred the standard images although some features including cardiac motion were equivalently rated. CONCLUSION: Real-time functional CMR with through-time radial GRAPPA performed without ECG-gating under free-breathing can be considered as an alternative to gold-standard breathhold cine imaging for the evaluation of ejection fraction in patients

Trans-Ethnic Mapping of BANK1 Identifies Two Independent SLE-Risk Linkage Groups Enriched for Co-Transcriptional Splicing Marks

BANK1 is a susceptibility gene for several systemic autoimmune diseases in several populations. Using the genome-wide association study (GWAS) data from Europeans (EUR) and African Americans (AA), we performed an extensive fine mapping of ankyrin repeats 1 (BANK1). To increase the SNP density, we used imputation followed by univariate and conditional analysis, combinedwith a haplotypic and expression quantitative trait locus (eQTL) analysis. The data from Europeans showed that the associated region was restricted to a minimal and dependent set of SNPs covering introns two and three, and exon two. In AA, the signal found in the Europeans was split into two independent effects. All of the major risk associated SNPs were eQTLs, and the risks were associated with an increased BANK1 gene expression. Functional annotation analysis revealed the enrichment of repressive B cell epigenomicmarks (EZH2 and H3K27me3) and a strong enrichment of splice junctions. Furthermore, one eQTL located in intron two, rs13106926, was found within the binding site for RUNX3, a transcriptional activator. These results connect the local genome topography, chromatin structure, and the regulatory landscape of BANK1 with co-transcriptional splicing of exon two. Our data defines a minimal set of risk associated eQTLs predicted to be involved in the expression of BANK1 modulated through epigenetic regulation and splicing. These findings allow us to suggest that the increased expression of BANK1 will have an impact on B-cell mediated disease pathways.The work presented in this paper has been supported by the Ministerio de Economía y Competitividad, Spain (SAF2016-78631-P), partly co-financed by FEDER funds of the European Union, the Gustaf den V:e-80-års Fond and the Swedish Association against Rheumatism to M.E.A-R. In addition, this work was financed by the NIH P01 grant P01-AI-083194 to C.D.L., J.B.H., R.K., and M.E.A-R. JBH: NIH grants: R01 AI024717, U01 HG00866, P30 AR070549 and U01 AI130830 and the US Department of Veterans Affairs: I01 BX001834.C.D.L.: Center for Public Health Genomics. R.K.: NIH grant R01-AR33062. J.A.J.: NIH grants U54GM104938, P30AR053483

Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71×10-34, OR = 1.43[1.26-1.60]) and rs1234317-T (P = 1.16×10-28, OR = 1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait. © 2013 Manku et al

Common Variants within MECP2 Confer Risk of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a predominantly female autoimmune disease that affects multiple organ systems. Herein, we report on an X-chromosome gene association with SLE. Methyl-CpG-binding protein 2 (MECP2) is located on chromosome Xq28 and encodes for a protein that plays a critical role in epigenetic transcriptional regulation of methylation-sensitive genes. Utilizing a candidate gene association approach, we genotyped 21 SNPs within and around MECP2 in SLE patients and controls. We identify and replicate association between SLE and the genomic element containing MECP2 in two independent SLE cohorts from two ethnically divergent populations. These findings are potentially related to the overexpression of methylation-sensitive genes in SLE

The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility. We studied IFNK single nucleotide polymorphisms (SNPs) in 3982 SLE cases and 4275 controls, composed of European (EA), African-American (AA), and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio = 1.93, P = 2.5 × 10−4), but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific. IFNK SNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association between IFNK SNPs and SLE and skin phenotypes. The serum IFN association suggests that IFNK variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin

Preferential binding to elk-1 by sle-associated il10 risk allele upregulates il10 expression

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans