Dataset Information

Baseline Objective Inflammation by Magnetic Resonance Imaging as a Predictor of Therapeutic Benefit in Early Rheumatoid Arthritis With Poor Prognosis.

ABSTRACT: OBJECTIVE:High magnetic resonance imaging (MRI)-detected inflammation is associated with greater progression and poorer outcomes in rheumatoid arthritis (RA). This analysis aimed to determine if baseline MRI inflammation was related to clinical response and remission in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) study. METHODS:AVERT was a phase IIIb, randomized, controlled trial with a 12-month, double-blind treatment period enrolling patients with early (?2 years' duration), anti-citrullinated peptide-positive methotrexate (MTX)-naive RA. In this post hoc analysis, patients in the abatacept plus MTX (n = 114) and MTX (n = 111) arms with available MRI results were stratified into low and high baseline MRI inflammation groups based on previously developed cutoffs of synovitis and osteitis on unilateral hand-wrist contrast-enhanced MRI. Simplified Disease Activity Index (SDAI) remission (?3.3), Clinical Disease Activity Index (CDAI) remission (?2.8), Boolean remission, and Disease Activity Score in 28 joints using the C-reactive protein level (<2.6) were assessed. RESULTS:Overall, 100 of 225 patients (44.4%) had high baseline MRI inflammation. In patients with high baseline MRI inflammation, a significantly greater proportion achieved remission at 12 months with abatacept plus MTX versus MTX across SDAI (45.1% versus 16.3%; P = 0.0022), CDAI (47.1% versus 20.4%; P = 0.0065), and Boolean indices (39.2% versus 16.3%; P = 0.0156). In patients with low baseline MRI inflammation, remission rates were not significantly different with abatacept plus MTX versus MTX (SDAI: 39.7% versus 32.3%; P = 0.4961). CONCLUSION:In seropositive, MTX-naive patients with early RA and presence of objectively measured high inflammation by MRI, indicating poor prognosis, remission rates were higher with abatacept plus MTX treatment versus MTX.

SUBMITTER: Ahmad HA

PROVIDER: S-EPMC7383909 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Baseline Objective Inflammation by Magnetic Resonance Imaging as a Predictor of Therapeutic Benefit in Early Rheumatoid Arthritis With Poor Prognosis.

Ahmad Harris A HA Baker Joshua F JF Østergaard Mikkel M Emery Paul P Durez Patrick P Ye June J Banerjee Subhashis S Conaghan Philip G PG

Arthritis care & research 20200526 7

<h4>Objective</h4>High magnetic resonance imaging (MRI)-detected inflammation is associated with greater progression and poorer outcomes in rheumatoid arthritis (RA). This analysis aimed to determine if baseline MRI inflammation was related to clinical response and remission in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) study.<h4>Methods</h4>AVERT was a phase IIIb, randomized, controlled trial with a 12-month, double-blind treatment period enrolling patients with early (≤2 y ...[more]

PMID: 31549793

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Project description:OBJECTIVE:Heart failure is a major contributor to cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA), but little is known about myocardial structure and function in this population. This study was undertaken to assess the factors associated with progression to heart failure in patients with RA. METHODS:With the use of cardiac magnetic resonance imaging, measures of myocardial structure and function were assessed in men and women with RA enrolled in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis study, a cohort study of subclinical cardiovascular disease in patients with RA, in comparison with non-RA control subjects from a cohort enrolled in the Baltimore Multi-Ethnic Study of Atherosclerosis. RESULTS:Measures of myocardial structure and function were compared between 75 patients with RA and 225 frequency-matched controls. After adjustment for confounders, the mean left ventricular mass was found to be 26 gm lower in patients with RA compared with controls (P < 0.001), an 18% difference. In addition, the mean left ventricular ejection fraction, cardiac output, and stroke volume were modestly lower in the RA group compared with controls. The mean left ventricular end systolic and end diastolic volumes did not differ between the groups. In patients with RA, higher levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and current use of biologic agents, but not other measures of disease activity or severity, were associated with significantly lower adjusted mean values for the left ventricular mass, end diastolic volume, and stroke volume, but not with ejection fraction. The combined associations of anti-CCP antibody level and biologic agent use with myocardial measures were additive, without evidence of interaction. CONCLUSION:These findings suggest that the progression to heart failure in RA may occur through reduced myocardial mass rather than hypertrophy. Both modifiable and nonmodifiable factors may contribute to lower levels of left ventricular mass and volume.

Project description:BackgroundThe long non-coding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) has been studied in many cancers, yet its relationship with colorectal cancer (CRC) remains poorly defined. Here, we conducted an analysis of The Cancer Genome Atlas (TCGA) database to better clarify the role of PCAT6 in this cancer type.MethodsWilcoxon rank-sum tests were utilized to assess relative levels of PCAT6 in CRC tumors and normal tissues, while logistic regression analyses were utilized to compare the relationships between PCAT6 levels and clinicopathological findings. Kaplan-Meier curves and Cox regression analyses were used to gauge correlations between PCAT6 and patient survival outcomes, while the biological roles of this lncRNA were investigated via a gene set enrichment analysis (GSEA) approach. The expression level of PCAT6 in CRC cell lines was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsPCAT6 levels were significantly correlated with CRC patient lymph node metastasis (N) stage [odds ratio (OR) =1.8 for N1 & N2 vs. N0], lymphatic invasion [OR =1.9 for yes vs. no), distant metastasis (M stage) (OR =2.1 for M1 vs. M0), carcinoembryonic antigen (CEA) level (OR =1.9 for >5 vs. ≤5), perineural invasion (OR =1.9 for yes vs. no), pathologic stage (OR =1.9 for stage III/IV vs. stage I/II), and neoplasm type (OR =2.1 for rectal adenocarcinoma vs. colon adenocarcinoma) (all P<0.05). CRC patients expressing higher PCAT6 levels exhibited poorer survival outcomes than those expressing low levels of this lncRNA (P=0.017), and in univariate analyses, higher PCAT6 levels were linked to worse overall survival [hazard ratio (HR) =1.540; 95% confidence interval (CI): 1.079-2.199; P=0.017], with this relationship also being preserved in a multivariate analysis (HR =6.892; 95% CI: 1.713-27.727, P=0.007). GSEA revealed high PCAT6 expression to be linked to differential DNA methylation enrichment, with high PCAT6 levels being associated with changes in base excision repair, cellular senescence, G2/M DNA damage checkpoint, chromatin-modifying enzyme, and gene silencing by RNA activity. The high expression of lncRNA PCAT6 in CRC cell lines was demonstrated by PCR experiments.ConclusionsPCAT6 represents a promising prognostic biomarker of poor CRC patient survival outcomes, with DNA methylation and RNA-mediated gene silencing being potentially promising mechanistic pathways whereby this lncRNA may shape patient outcomes.

Dataset Information

Baseline Objective Inflammation by Magnetic Resonance Imaging as a Predictor of Therapeutic Benefit in Early Rheumatoid Arthritis With Poor Prognosis.

Publications

Baseline Objective Inflammation by Magnetic Resonance Imaging as a Predictor of Therapeutic Benefit in Early Rheumatoid Arthritis With Poor Prognosis.

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