Gadebramsen8558

studies are required to evaluate if CBI could serve as a marker of disease progression.Circular RNAs (circRNAs) have been implicated in the pathological regulation of human diseases by acting as microRNA (miRNA) sponges to affect gene expression. CircRNA Fragile Mental Retardation 2 (circ_AFF2) was dysregulated in rheumatoid arthritis (RA), but little is known about its specific function and hidden molecular mechanism in RA. Circ_AFF2, miR-375 and TAK1-binding 2 (TAB2) expression levels were determined through the quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was performed to analyze cell cycle and apoptosis. Cell proliferation detection was conducted by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The protein levels were measured using western blot. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). RNA pull-down assay was used to select the miRNA target of circ_AFF2. The interaction between miR-375 and circ_AFF2 or TAB2 was analyzed using the dual-luciferase reporter assay. Contrasted to normal samples and fibroblast-like synoviocytes (FLS), circ_AFF2 expression was upregulated in RA blood samples and FLS-RA cells. Cell cycle, proliferation and inflammatory response were blocked while apoptosis was promoted in FLS-RA after the downregulation of circ_AFF2. In addition, circ_AFF2 could interact with miR-375 and the function of circ_AFF2 was achieved by sponging miR-375 in FLS-RA cells. Moreover, TAB2 was a target of miR-375 and miR-375 repressed RA progression by decreasing TAB2 expression in FLS-RA cells. More importantly, circ_AFF2 promoted the expression of TAB2 by targeting miR-375. These findings clarified that circ_AFF2 induced cell progression, inflammatory response in FLS-RA cells via the miR-375/TAB2 axis. Circ_AFF2 could be used as a biomarker in the diagnosis and treatment of RA.

DROSHA and DICER1 enzymes participate in the main stages of microRNA synthesis. Polymorphisms can influence mRNAs stability and genes expression, and hence affect the binding of miRNAs. Thus, the present study evaluated the association of DROSHA and DICER1 polymorphisms in the development of endometriosis and other diseases.

A total of 240 endometriosis cases and 242 controls were genotyped for the DROSHA rs10719 G>A and DICER1 rs3742330 A>G polymorphisms using the TaqMan system. The association between polymorphisms and endometriosis was estimated by binary logistic regression. A literature review was also performed including all published articles (PubMed database) until December 2020, regarding the association of the studied polymorphisms and different diseases.

DICER1 rs3742330GG was only found in endometriosis cases (2.1%) and deep infiltrative endometriosis (DIE) (2.5%). The DICER1 rs3742330GG genotype was significantly associated with endometriosis (P<0.05), suggesting a tendency to presy different among populations, and there were discrepancies in the risk associations with the development of diseases.Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS One-hundred ninety-three patients (age 67 ± 11 years, QRS width 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI 2.10-9.06). CONCLUSIONS The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.

Patients having CYP2C19 loss-of-function alleles and receiving clopidogrel are at higher risk of adverse cardiovascular outcomes. Ticagrelor is an effective antiplatelet that is unaffected by the CYP2C19 polymorphism. The main aim of the current research is to evaluate the cost-effectiveness among CYP2C19 genotype-guided therapy, universal ticagrelor, and universal clopidogrel after a percutaneous coronary intervention (PCI).

A two-part decision-analytic model, including a one-year model and a 20-year follow-up Markov model, was created to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-effectiveness ratio (ICER, cost/success) and incremental cost-utility ratio (ICUR, cost/quality-adjusted life years [QALY]). Therapy success was defined as survival without myocardial infarction, stroke, cardiovascular death, stent thrombosis, and no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. The model was based on a multivariate analysis, and a sensitivity analysis confirmed the robustness of the model outcomes, including against variations in drug acquisition costs.

Against universal clopidogrel, genotype-guided therapy was cost-effective over the one-year duration (ICER, USD 6102 /success), and dominant over the long-term. Genotype-guided therapy was dominant against universal ticagrelor over the one-year duration, and cost-effective over the long term (ICUR, USD 1383 /QALY). Universal clopidogrel was dominant over ticagrelor for the short term, and cost-effective over the long-term (ICUR, USD 10,616 /QALY).

CYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy, followed by universal clopidogrel, and then universal ticagrelor for post-PCI patients in Qatar.

CYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy, followed by universal clopidogrel, and then universal ticagrelor for post-PCI patients in Qatar.

Clinicians evaluating acute PE patients often have to identify risks for massive PE, a measure of hemodynamic instability and its consequence, massive PE related adverse clinical events (PEACE). We investigated the association of these risk factors with massive PE and PEACE in a consecutive PE cohort (n=364).

Massive PE was defined as an acute central clot (proximal to the lobar artery) in a patient with right heart strain and systolic blood pressure≤90mg. PEACE was defined as any massive PE who died or required one or more of the following ACLS, assisted ventilation, vasopressor use, thrombolytic therapy, or invasive thrombectomy, within seven days of PE diagnosis. Univariate and multivariate analysis assessing associations between the risk factors (age, gender, comorbidities, PE provoking risks, and whether the PE was felt to be idiopathic) and massive PE or PEACE were performed. Significance was determined at p<0.05.

Thirteen percent (n=48) of patients presented with massive PE, and 9% (n=32) had PEACE. In the final multivariate model, recent invasive procedure (RR=7.4, p=0.007), recent hospitalization (RR=7.3, p=0.002), and idiopathic PE (RR=6.5, p=0.003) were associated with massive PE. Only idiopathic PE (RR=5.7, p=0.005) was significantly associated with PEACE. No comorbidities or other PE provoking risks were associated with massive PE or PEACE.

As a take-home message, recent invasive procedure, recent hospitalization, and idiopathic PE were associated with massive PE, and only idiopathic PE was associated with PEACE. TED-347 Simultaneously, comorbidities like age or chronic cardiopulmonary disease seem not to be associated with massive PE or PEACE.

As a take-home message, recent invasive procedure, recent hospitalization, and idiopathic PE were associated with massive PE, and only idiopathic PE was associated with PEACE. Simultaneously, comorbidities like age or chronic cardiopulmonary disease seem not to be associated with massive PE or PEACE.

Heart failure (HF) hospitalizations remains a significant burden on the health care system. Stimulants including cocaine, amphetamine and its derivatives are amongst the most used illegal substances in the United States. The information regarding stimulant-related HF hospitalizations is scarce. We sought to evaluate the characteristics and trends of stimulant-related HF hospitalizations in the United States and their associated outcomes and resource utilization.

Using the National Inpatient Sample (NIS), we identified patients with a primary diagnosis of HF hospitalization. These hospitalizations were further divided into those with and without a concomitant diagnosis of stimulant (cocaine or amphetamine) dependence or abuse. Survey specific techniques were employed to compare trends in baseline characteristics, complications, procedures, outcomes and resource utilization between the two cohorts.

We identified 9,932,753 hospitalizations (weighted) with a primary diagnosis of heart failure, of those 138,438 (1.39%) had a diagnosis of active stimulant use. The proportion of stimulant-related HF hospitalization is on the rise (1.1% to 1.9%). Stimulant-related HF hospitalization was highest amongst age group 30-39years and 7.9% of HF hospitalizations in this age group were due to stimulant use. The proportion of stimulant-related HF hospitalization for the White and Hispanic race has doubled from 2008 to 2017. Stimulant-related HF hospitalization is associated with increased incidence of in-hospital complications like cardiogenic shock, acute kidney injury and ventricular tachycardia. These patients have more than 7-fold higher discharge against medical advice.

Stimulant-related HF hospitalizations have been increasing. It is associate with significant morbidity burden and health care utilization.

Stimulant-related HF hospitalizations have been increasing. It is associate with significant morbidity burden and health care utilization.

Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials.

To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use.

MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites.

T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R

>0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.