94 research outputs found
Association of Complement and MAPK Activation With SARS-CoV-2-Associated Myocardial Inflammation
IMPORTANCE Myocardial injury is a common feature of patients with SARS-CoV-2 infection. However, the cardiac inflammatory processes associated with SARS-CoV-2 infection are not completely understood. OBJECTIVE To investigate the inflammatory cardiac phenotype associated with SARS-CoV-2 infection compared with viralmyocarditis, immune-mediatedmyocarditis, and noninflammatory cardiomyopathy by integrating histologic, transcriptomic, and proteomic profiling. DESIGN, SETTING, AND PARTICIPANTS This case serieswas a cooperative study between the Ludwig Maximilian University Hospital Munich and the Cardiopathology Referral Center at the University of Tubingen in Germany. A cohort of 19 patients with suspectedmyocarditis was examined; of those, 5 patients were hospitalized with SARS-CoV-2 infection between March and May 2020. Cardiac tissue specimens from those 5 patients were compared with specimens from 5 patients with immune-mediatedmyocarditis, 4 patients with non-SARS-CoV-2 viralmyocarditis, and 5 patients with noninflammatory cardiomyopathy, collected from January to August 2019. EXPOSURES Endomyocardial biopsy. MAIN OUTCOMES AND MEASURES The inflammatory cardiac phenotypeswere measured by immunohistologic analysis, RNA exome capture sequencing, and mass spectrometry-based proteomic analysis of endomyocardial biopsy specimens. RESULTS Among 19 participants, the median age was 58 years (range, 37-76 years), and 15 individuals (79%) were male. Data on race and ethnicity were not collected. The abundance of CD163+ macrophages was generally higher in the cardiac tissue of patients with myocarditis, whereas lymphocyte counts were lower in the tissue of patients with SARS-CoV-2 infection vs patients with non-SARS-CoV-2 virus-associated and immune-mediatedmyocarditis. Among those with SARS-CoV-2 infection, components of the complement cascade, including C1q subunits (transcriptomic analysis: 2.5-fold to 3.6-fold increase; proteomic analysis: 2.0-fold to 3.4-fold increase) and serine/cysteine proteinase inhibitor clade G member 1 (transcriptomic analysis: 1.7-fold increase; proteomic analysis: 2.6-fold increase), belonged to the most commonly upregulated transcripts and differentially abundant proteins. In cardiac macrophages, the abundance of C1q was highest in SARS-CoV-2 infection. Assessment of important signaling cascades identified an upregulation of the serine/threonine mitogen-activated protein kinase pathways. CONCLUSIONS AND RELEVANCE This case series found that the cardiac immune signature varied in inflammatory conditions with different etiologic characteristics. Future studies are needed to examine the role of these immune pathways inmyocardial inflammation
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 protocolâ61 % male, with mean age of 64 ± 8.2 years. SAS was highest in those with cardiovascular disease without diabetes [10.1 (0â39.5)], followed by those with T2DM and CVD [4 (0â41.1)], then those with T2DM only [3.23 (0â19.4)] with healthy controls having the lowest atheroma score [2.4 (0â19.4)]. 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 (4â19) vs. 2.8 (0â17), 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
The GOLMePsA study protocol: an investigator-initiated, double-blind, parallel-group, randomised, controlled trial of GOLimumab and methotrexate versus methotrexate in early diagnosed psoriatic arthritis using clinical and whole body MRI outcomes
Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis which impacts significantly on the quality of life and work capacity of affected individuals. Recent evidence has shown that early control of inflammation in PsA leads to improved long-term outcomes. It is postulated that prompt intervention after diagnosis using a remission-induction treatment strategy will lead to improved outcomes and optimal disease control of PsA. The aim of the present study was to compare the clinical efficacy of a treatment strategy in newly diagnosed, treatment naĂŻve PsA subjects, using the combination of golimumab (GOL), methotrexate (MTX) and steroids versus standard care (MTX monotherapy plus steroids). Methods/design: GOLMePsA is an investigator initiated, phase IIIb, single-centre, randomised, double-blind, placebo-controlled, two-armed, parallel-group, imaging-supplemented study. Eighty-eight PsA patients, diagnosed within 24 months prior to screening and treatment naĂŻve, will be randomised at baseline to receive: (arm 1) the combination of intramuscular/intra-articular prednisolone, MTX and GOL or (arm 2) the combination of intramuscular/intra-articular prednisolone, MTX and placebo for 24 weeks (interventional period). Primary outcome measure is clinical improvement (at least 1 unit difference) in the Psoriatic ArthritiS Disease Activity Score (PASDAS) composite index. Reflecting a âstep downâ therapeutic approach, all participants successfully completing the interventional period will be followed up for a further 28 weeks. During this observational period, stable maintenance MTX monotherapy will continue for both arms, unless in case of intolerance or PsA relapse. In the latter case, additional treatment will be provided. Overall, the GOLMePsA study length is planned to be 52 weeks. Discussion: The hypothesis underlining this study is that very early treatment with first-line GOL reduces disease activity in PsA, in comparison to conventional therapy. Trial registration: EudraCT 2013â004122-28. 24/09/2013
Mesenchymal stem cells in cardiac regeneration: a detailed progress report of the last 6Â years (2010â2015)
Kalziumphosphat versus Polymethylmethacrylat: Ergebnisse einer prospektiven, randomisierten, klinischen Vergleichsstudie zur perkutanen Ballon-Kyphoplastie
FrĂŒhzeitige in vivo Stabilisierung und Biointegration eines injizierbaren Komposits aus BMP-7 und Kalziumphosphat. Eine radiologische und biomechanische Untersuchung an der LendenwirbelsĂ€ule des Schafs
- âŠ