bluuebunny/crossref_metadata_2025_split huggingface dataset:
AQbD-Oriented UHPLC/MS/MS Method Development for Glycopeptides Assessment in Pharmaceutical Forms
Authors: Stajić A , Janković-Maksić J , Jančić-Stojanović B , Medenica M 
Published: February 2021

Abstract
Vancomycin and teicoplanin are glycopeptide antibacterials that inhibit the bacteria cell wall synthesis showing activity against gram-positive bacteria.
Development of the sensitive method is of great importance for quality control of these drugs that are fermentation products. Modification of the fermentation conditions could cause the differences in the relative amount of the total substance or component, as it is the case with teicoplanin. The main objective of this study was development of the sensitive and effective ultra high performance liquid chromatography - tandem mass sprectrometry (UHPLC-MS/MS) method for simultaneous quantification of vancomycin, all six subcomponents of teicoplanin, and its pharmacopoeial impurity A in pharmaceutical forms. The scientific-based Quality by Design approach was implemented in the MS and UHPLC method development. Detection and quantification of analytes were carried out in positive electrospray ion mode by multiple reaction monitoring. Capillary voltage, cone voltage and collision energy were optimized by implementing experimental design methodology and optimal values for each fragment ion were obtained by performing experiments according to ‘Rechtschaffen’ design matrix. An ACQUITY CSH Phenyl-hexyl (2.1 × 50 mm, particle size 1.7 μm) column was chosen for the separation under the gradient elution mode with the mobile phase consisted of 0.1% formic acid in water (mobile phase A) and acetonitrile (mobile phase B). Optimal gradient elution parameters were achieved by applying ‘Rechtschaffen’ design too. Method operable design regions were constructed for investigated MS and chromatographic parameters. The method was fully validated, and its applicability was confirmed throughout the ability to follow the behavior of vancomycin and teicoplanin under stress conditions.
miR-24-3p regulates CDX2 during intestinalization of cardiac-type epithelium in a human model of Barrett’s esophagus
Authors: Gil-Gómez Gabriel , Fassan Matteo , Nonell Lara , Garrido Marta , Climent Marta , Anglada Roger , Iglesias Mar , Guzzardo Vicenza , Borga Chiara , Grande Luis , de Bolós Carme , Pera Manuel 
Published: February 2021

SummaryBackgroundCardiac-type epithelium has been proposed as the precursor of intestinal metaplasia in the development of Barrett’s esophagus. Dysregulation of microRNAs (miRNAs) and their effects on CDX2 expression may contribute to intestinalization of cardiac-type epithelium. The aim of this study was to examine the possible effect of specific miRNAs on the regulation of CDX2 in a human model of Barrett’s esophagus.MethodsMicrodissection of cardiac-type glands was performed in biopsy samples from patients who underwent esophagectomy and developed cardiac-type epithelium in the remnant esophagus. OpenArray™ analysis was used to compare the miRNAs profiling of cardiac-type glands with negative or fully positive CDX2 expression. CDX2 was validated as a miR-24 messenger RNA target by the study of CDX2 expression upon transfection of miRNA mimics and inhibitors in esophageal adenocarcinoma cell lines. The CDX2/miR-24 regulation was finally validated by in situ miRNA/CDX2/MUC2 co-expression analysis in cardiac-type mucosa samples of Barrett’s esophagus.ResultsCDX2 positive glands were characterized by a unique miRNA profile with a significant downregulation of miR-24-3p, miR-30a-5p, miR-133a-3p, miR-520e-3p, miR-548a-1, miR-597-5p, miR-625-3p, miR-638, miR-1255b-1, and miR-1260a, as well as upregulation of miR-590-5p. miRNA-24-3p was identified as potential regulator of CDX2 gene expression in three databases and confirmed in esophageal adenocarcinoma cell lines. Furthermore, miR-24-3p expression showed a negative correlation with the expression of CDX2 in cardiac-type mucosa samples with different stages of mucosal intestinalization.ConclusionThese results showed that miRNA-24-3p regulates CDX2 expression, and the downregulation of miRNA-24-3p was associated with the acquisition of the intestinal phenotype in esophageal cardiac-type epithelium.
Impact on clinical outcomes of right ventricular response to percutaneous correction of secondary mitral regurgitation
Authors: Caiffa T , Castrichini M , Biagini E , De Luca A , Compagnone M , Berardini A , Merlo M , Fabris E , Vitrella G , Pinamonti B , Korcova R , Barbati G , Saia F , Stolfo D , Sinagra G 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Background. Right ventricular function (RVF) is a strong determinant of prognosis in patients with reduced ejection fraction heart failure (HFrEF) and secondary mitral regurgitation (SMR). Percutaneous mitral valve repair (pMVR) can promote the recovery of RVF.
Purpose. We sought to characterize the RV response to pMVR in HFrEF with SMR and to assess the influence of improved RVF after pMVR in this specific setting of patients.
Methods. We included all the patients with HFrEF and SMR≥3+ successfully treated with pMVR between April 2012 and January 2020 in two tertiary care centers for HF. Improved RVF was defined as DRVFAC≥5% at early follow-up (median time 4 months). The primary endpoint was a composite of death/heart transplant (D/HT).
Results. In total, 110 patients were included. Mean age was 67 ± 12 years, mean LVEF was 31 ± 8% and mean RVFAC was 31 ± 10%. DRVFAC≥5% occurred in 54 (49%) patients and was independent from the measures of left ventricle recovery. During a median follow-up of 36 months (IQR 19-52), 40 patients (36%) died or were transplanted. After adjustment for other significant covariates, DRVFAC≥5% was significantly associated with lower risk of D/HT (HR 0.49, 95% CI 0.24 – 0.98 p &lt; 0.042) along with M2+ at follow-up (HR 0.36; 95% CI 0.17-0.74 p 0.005).
Conclusions. In patients with HFrEF and SMR, the improvement of RVF is frequent after pMVR and is associated with better long-term survival free from HT.
Abstract Figure.
Evaluation of left atrial volume in obesity. How indexation by body surface compares to indexation by height
Authors: Azzari F , Krsticevic L , Dionne N , Veilleux SP , Rioux L 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background

Left atrial enlargement (LAE) is a risk factor for atrial fibrillation, stroke and heart failure with preserved ejection fraction. Current ASE/EACVI guidelines recommend indexing left atrial volume (LAV) by body surface area (BSA) for LAE grading. However, in overweight patients, this ratio must be interpreted with caution due to a disproportionate increase in BSA.

Purpose

We have assessed LAE in overweight (OW), obese (OB) and severely obese (SO) patients by indexing LAV by height (Ht) instead of BSA.

Methods

We retrospectively evaluated LAV in 1246 patients from our echocardiography clinic.
We graded LAE by BSA, in patients with a normal body mass index (BMI ≥18.5 and &lt;25 kg/m², n = 422). Afterwards, we established the cut-offs for the LAV/Ht ratio by the receiver operating curve (ROC) method. We reported sensitivity (Se), specificity (Sp), area under ROC curve (AUC) and Youden’s index (Yi).
Finally, we applied the LAV/Ht ratio to OW (BMI ≥25 and &lt;30 kg/m², n = 467), OB (BMI ≥30 and &lt;35 kg/m², n = 235) and SO (BMI ≥35 kg/m², n = 122) patients.

Results

There were no differences in Ht between groups. As expected, the weight (63.2 ± 8.8, 77.4 ± 9.6, 91.7 ± 11.5 and 110.4 ± 17.3 kg) and BSA were significantly different in between groups.
The cut-offs for the LAV/Ht ratio were ≥35 ml/m (Se 96.3%, Sp 97.3%, AUC 0.997, Yi 0.94), ≥42 ml/m (Se 100%, Sp 96.7%, AUC 0.996, Yi 0.97) and ≥48 ml/m (Se 94.3%, Sp 97.0%, AUC 0.954, Yi 0.94) for mild, moderate and severe LAE, respectively.
The table shows LAV and LAE grading according to BMI group. When applying the LAV/Ht ratio, the LAE grade increased in 29.8% of OW, 48.5% of OB and 66.4% of SO patients.
Conclusion(s):
LAV is significantly increased in OW, OB, and SO patients.
In this population, the LAV/BSA ratio significantly underestimates the degree of LAE. The LAV/Ht ratio allows an accurate categorization of LAV, leading to a significant reclassification of LAE.
Normal Weight Overweight Obese Severely Obese LAV (ml) ¶ 58.3 ± 26.4 63.5 ± 24.0 69.3 ± 25.7 76.4 ± 25.1 LAV/BSA (ml/m2) 33.9 ± 14.2 33.8 ± 12.1 34.3 ± 11.9 35.3 ± 10.7 Normal / Mild 64.5 / 15.4% 63.2 / 19.3% 64.3 / 16.2% 54.1 / 23.8% Moderate / Severe 7.6 / 12.6% 6.9 / 10.7% 8.9 / 10.6% 10.7 / 11.5% LAV/Ht (ml/m) 34.7 ± 15.0 37.6 ± 13.6 41.0 ± 14.6 45.9 ± 14.4 Normal / Mild – 50.3 /20.1% 39.1 / 25.1% 21.3 / 23.0% Moderate / Severe – 13.9 / 15.6% 13.2 / 22.6% 18.9 / 36.9% ¶ ANOVA between BMI groups: &lt;0.0001; Comparison between LAE grading by BSA or Ht: OW χ²=22.4, p = 0.0001; OB χ²=30.8, p &lt; 0.0001; SO χ²=36.5, p = 0.0001
Echocardiographic phenotypes of patients with sickle cell disease. An unsupervised analysis based on etendard cohort
Authors: D"humieres T , Inamo J , Deswarte S , Damy T , Loko G , Lionnet F , Humbert M , Derumeaux G , Savale L , Bartolucci P 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PHRC

Backgroung
Echocardiography is the cornerstone in the diagnosis of cardiopulmonary involvement in sickle cell disease (SCD). However, given the unique pathophysiology of SCD associating high cardiac output, and various degrees of peripheral vasculopathy, differentiate the pathological from the physiological using echocardiography can be particularly challenging.

Purpose
This study sought to link cardiac phenotypes in homozygous SCD patients with clinical profiles and outcomes using cluster analysis.

Methods
We analyzed data of 379 patients with a sufficient echographic dataset included in the French Etendard Cohort, a prospective cohort initially designed to assess the prevalence of pulmonary hypertension. A cluster analysis was performed on echocardiographic variables, and the association between clusters and clinical profiles and outcomes was assessed.

Results
Three clusters were identified. Cluster 1 (N = 122) patients had the lowest cardiac output, only mild left cavities remodeling, diastolic dysfunction, and high tricuspid regurgitation velocity (TRV). They were predominantly female, as old as cluster 2, and displayed the most severe functional limitation. Cluster 2 (N = 103) patients had the highest cardiac output, left ventricular mass and a severely dilated left atrium. Diastolic function and TRV were similar to cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (N = 154) patients had mild left cavities remodeling, the best diastolic function and the lowest TRV. They were younger patients with the highest hemoglobin and lowest hemolytic markers. Right heart catheterization was performed in 94 patients. Cluster 1 gathered the majority of precapillary PH while cluster 2 gathered postcapillary PH and no PH was found in cluster 3. After a follow-up of 9.9 years (IQR: 9.3 to 10.5 years) death occurred in 38 patients (10%). Clusters 2 had the worst prognosis with 18% mortality rate vs. 12% in cluster 2 and 5% in cluster 1 (P log-rank = 0,02). Results are summarized in the central illustration.

Conclusions
Cluster analysis of echocardiographic variables identified 3 phenotypes among SCD patients, each associated with different clinical features and outcome. These findings underlines the necessity to rethink echocardiographic evaluation of SCD patients, with an integrative approach based on simultaneous evaluation of TRV along with left cavities remodeling and diastolic parameters.
Abstract Figure.
Reduction of left atrial strain and strain rate during conduit phase as the earliest marker of left ventricular diastolic disfunction
Authors: Savelev A , Solovev OV , Baturova MA , Shubik YV 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Left atrial (LA) functional abnormalities, including LA strain (LAS) and strain rate (LASR) reduction, are observed in patients with left ventricular diastolic disfunction (LVDD). However, the degree of reduction at different stages of LVDD is not fully clarified.
We aimed to assess the interdependence between LAS and LASR parameters and LVDD grades in subjects of advanced age with preserved ejection fraction (EF).

Material and methods
Consecutive patients, who underwent echocardiography within 12 months, were screened and included into the study in case of age older than 65 years, preserved EF, sinus rhythm at the time of study and preserved dataset of sufficient quality for speckle tracking analysis. LAS and LASR parameters, including LAS and peak LASR during reservoir, conduit, and contractile phases were calulated with single plane apical 4-chamber view assessment. One-way ANOVA analysis with Bonferroni correction was used to assess the difference between groups.

Results
Among 153 patients (mean age 74 ± 7 years; 105 female, mean EF 64 ± 5%) included in the study there were 38 patients with no evidence of LVDD, 67 with LVDD grade 1, 40 with LVDD grade 2, and 5 with LVDD grade 3. The values of LAS and LASR parameters for these groups are summarized in Table. All parameters were significantly reduced in grade 2 and 3 LVDD patients comparing to the patients with no LVDD. Contractile phase LAS and LASR were slightly higher in grade 1 than in no LVDD patients. Reservoir and conduit phase LAS and LASR were lower in grade 1 LVDD comparing to no LVDD, but only for conduit phase parameters the difference was significant. In ROC analysis for conduit phase LAS and LASR to be associated with the presence of LVDD of any grade the area under the curve was 0,707 (p &lt; 0.001) and 0,742 (p &lt; 0.001) respectively.

Conclusion
Impaired LA function is seen in patients with LVDD. Whereas measurements characterizing LA reservoir and contractile functions demonstrate significant decrease at advanced stages of LVDD, conduit function is significantly reduced at grade 1 LVDD, providing the possibility for early detection of LVDD.
Group LAS (%) LASR (1/sec) reservoir conduit contractile reservoir conduit contractile No LVDD, n = 38 29,7 ± 9,3 †‡ 15,1 ± 6,6 §†‡ 14,6 ± 5,4 †‡ 1,28 ± 0,37 †‡ 1,18 ± 0,44 §† 1,68 ± 0,60 †‡ Grade 1, n = 69 28,6 ± 8,9 †‡ 11,6 ± 6,2 ƒ 17,0 ± 5,7 †‡ 1,23 ± 0,43 ‡ 0,90 ± 0,38 ƒ 1,99 ± 0,71 †‡ Grade 2, n = 40 19,1 ± 7,1 ƒ§ 9,2 ± 4,5 ƒ 9,9 ± 4,4 ƒ§ 0,87 ± 0,26 ƒ§ 0,72 ± 0,27 ƒ 1,07 ± 0,44 ƒ§ Garde 3, n = 5 13,8 ± 3,6 ƒ§ 7,7 ± 2,5 ƒ 6,1 ± 2,2 ƒ§ 0,8 ± 0,29 ƒ 0,75 ± 0,28 0,67 ± 0,27 ƒ§ Significant difference (p &lt; 0,05): ƒ – with No LVDD, § – with Grade 1 LVDD, † – with Grade 2 LVDD, ‡ – with Grade 3 LVDD
Prognostic role of myocardial work in patients with heart failure and reduced ejection fraction treated by sacubitril/valsartan
Authors: Galli E , Bouali Y , Gallard A , Hubert A , Leclercq C , Donal E 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
the non-invasive assessment of myocardial work (MW) by pressure-strain loops analysis (PSL) is a relative new tool for the evaluation of myocardial performance. Sacubitril/Valsartan is a treatment for heart failure with reduced ejection fraction (HFrEF) which has a spectacular effect on the reduction of cardiovascular events (MACEs).
Purposes of this study were to evaluate 1) the short and medium term effect of Sacubitril/Valsartan treatment on MW parameters; 2) the prognostic value of MW in this specific group of patients.

Methods
79 patients with HFrEF (mean age: 66 ± 12 years; LV ejection fraction: 28 ± 9%) were prospectively included in the study and treated with Sacubitril/Valsartan. Echocardiographic examination was performed at baseline, and after 6- and 12-month of therapy with Sacubitril/Valsartan.

Results
Sacubitril/Valsartan significantly increased myocardial constructive work (CW) (1023 ± 449 vs 1424 ± 484 mmHg%, p &lt; 0.0001) and myocardial work efficiency (WE) [87 (78-90) vs 90 (86-95), p &lt; 0.0001]. During FU (2.6 ± 0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LVEF and WE, global myocardial constructive work (CW) was the only predictor of MACEs [HR 0.99 (0.99-1.00), p = 0.05]. (Table 1). A CW &lt; 910 mmHg (AUC = 0.81, p &lt; 0.0001, Figure 1, left panel) identified patients at particularly increase risk of MACEs [HR 11.09 (1.45-98.94), p = 0.002, log-rank test p &lt; 0.0001] (Figure 2, Right panel).

Conclusions
in patients with HFrEF who receive a comprehensive background beta-blocker and mineral-corticoid receptor antagonist therapy, Sacubitril/Valsartan induces a significant improvement of myocardial CW and WE. In this population, the estimation of CW before the initiation of Sacubitril/Valsartan therapy allows the prediction of MACEs.
Univariable analysis Multivariable analysis HR (95% CI) p-value HR (95% CI) p-value Age, per year 0.99 (0.95-1.04) 0.81 Ischemic cardiomyopathy 1.07 (0.36-3.21) 0.89 LVEDVi*, per ml/m2 1.01 (1.00-1.03) 0.03 LVESVi, per ml/m2 1.01 (1.00-1.03) 0.009 1.01 (0.99-1.02) 0.35 LVEF, per % 0.91 (0.85-0.98) 0.01 1.02 (0.93-1.12) 0.71 CW, per mmHg% 0.99 (0.99-1.00) 0.002 0.99 (0.99-1.00) 0.04 WE, per mmHg% 0.91 (0.86-0.96) 0.001 0.95 (0.88-1.02) 0.16 Predictors of MACEs at univariable and multivariable analysis Abstract Figure 1 A and B
Shear wave elastography: can we discover elevated diastolic filling pressures?
Authors: Werner AE , Bezy S , Orlowska M , Kubiak G , Duchenne J , Desmet W , Delcroix M , Van Cleemput J , Ince H , D"hooge J , Voigt JU 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public hospital(s). Main funding source(s): University Hospitals (Uz) Leuven

Background
The assessment of the left ventricular diastolic function is complex, as there is no single invasive parameter that provides a direct measurement of myocardial relaxation, myocardial compliance, or – as a surrogate - LV filling pressure. Estimation of diastolic function is therefore based on the combination of several parameters.
Shear wave (SW) elastography is a novel method based on high frame rate echocardiography. SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC), and their propagation velocity is directly related to myocardial stiffness (MS).

Purpose
The aim of this study was to investigate if velocities of natural shear waves are related to MS at end-diastole (ED) and, thus, could be used to estimate left ventricular end-diastolic pressures (LVEDP) as marker of diastolic function.

Methods
So far, we have prospectively enrolled 42 patients with a wide range of diastolic function, scheduled for heart catheterization so that LV filling pressures could be invasively measured. Patients with severe aortic stenosis, mitral stenosis of any degree and a more than moderate mitral regurgitation, as well as regional myocardial abnormalities or dysfunction in the anteroseptal wall were excluded.
Echocardiography was performed immediately after catheterization. SW elastography in parasternal long axis views of the left ventricle (LV) was performed using an experimental scanner (HD-PULSE) at 1100 ± 250 frames per second. Tissue acceleration maps were extracted from an anatomical M-mode line along the midline of the LV septum. The SW propagation velocity at MVC was measured as the slope on the M-mode acceleration map (Figure A). Standard echocardiographic parameters of diastolic function were obtained with a high end ultrasound machine.

Results
SW velocities at ED correlated well with the invasively measured LVEDP (r = 0.74, p &lt; 0.001, Figure B). In comparison, classical echocardiographic parameters correlated only weakly with LVEDP (E/A: r = 0.398, p = 0.02, Figure C; E/E’: r = 0.204, p = 0.247, Figure D).
For the detection of an elevated LVEDP above 15 mmHg, a cut off value for the SW velocity at MVC of 4.395 m/s (Figure A) was associated with a sensitivity of 91.3% and a specificity of 90.9%.

Conclusions
End-diastolic shear wave velocities, measured by high frame rate shear wave elastography, showed a significant correlation with the end-diastolic filling pressure of the LV and allowed to differentiate normal from elevated filling pressure which indicates a potential clinical value of the new method for a non-invasive and direct assessment of LV diastolic function. More patients will be included to confirm these findings.
Abstract Figure.
Multivariate analysis of right ventricle echocardiographic function parameters for the prediction of outcomes in significant functional tricuspid regurgitation
Authors: Travieso Gonzalez A , Romero Delgado T , Luque Diaz TS , Islas F , Olmos C , Higueras Nafria J , Vivas D , Mahia Casado P , Vilacosta I 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Functional tricuspid regurgitation is a common disease that significantly impairs survival and quality of life. The role of echocardiographic right ventricular (RV) function parameters to detect patients with worse prognosis that may benefit from invasive treatment is still under debate.

Methods
121 consecutive patients with grade III and IV functional tricuspid regurgitation were evaluated. RV function parameters and clinical variables were assessed at baseline, and then patients were prospectively followed-up. The primary endpoint was the combination of death or heart failure (HF) admissions. Comparison of imaging parameters was done using receiver-operating characteristics (ROC) curves. Multivariate logistic regression analysis was preformed to establish independent predictors of outcomes.

Results
Median follow up was 27.3 months. 73.6% of the patients were female, and mean age was 80.4 years. 63.6% were grade IV tricuspid regurgitation.
In the univariate analysis using the area under the ROC curve (AUC), RV-free wall strain (RVS, AUC = 0.633) and pulmonary artery systolic pressure (PASP, AUC = 0.605) were the best predictors of death and HF admissions, showing better diagnostic performance than tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and tricuspid S’ (p &lt; 0.001 for each comparison) (graph 1A).
In the multivariate analysis including either clinical and echocardiographic variables, independent predictors of death and HF admissions were Age (OR 1.07, p = 0.029), RVS&gt;-16 (OR 5.0, p = 0.001), Diabetes mellitus (OR 3.0, p = 0.011), eGFR (ml/min, OR 0.96, p = 0.001) and Hemoglobin (g/dL, OR = 0.74, p = 0.048) (table 1). The model including these variables was superior than RVS and PASP alone (AUC 0.884, p &lt; 0.001) (graph 1B), showing high sensitivity (78.8%) and moderate specificity (67.3%).

Conclusions
In patients with significant functional tricuspid regurgitation, RVS and PASP show the best performance for the detection of death and HF admissions. A multivariate model including age, diabetes, eGFR, hemoglobin and RVS was superior than the individual imaging parameters.
Table 1 Variable OR 95% CI P value Age (years) 1.07 1.01-1.13 0.029 Diabetes Mellitus 3.00 1.29-7.00 0.011 RV free wall strain &gt;-16 5.01 1.87-13.4 0.001 Hemoglobin (d/dL) 0.74 0.55-1.00 0.048 eGFR (ml/min) 0.96 0.94-0.98 0.001 OR odds ratio. CI: confidence interval. eGFR: estimated glomerular filtration rate (CKD-EPI formula). Abstract Figure. Graph 1