Notes

DHODH inhibition modulates glucose procedure circulating GDF15, along with increases metabolism stability.
ng gap in survival between AC and CC.
The efficacy of immune checkpoint inhibitors (ICIs) is low among EGFR-mutated non-small-cell lung cancer (NSCLC), although prolonged responses have occasionally been reported. We investigated the association between mutation subtypes and ICI outcomes among HER2- and EGFR-mutated NSCLC.

This retrospective single-center study analyzed patients with EGFR- and HER2-mutated advanced NSCLC who received at least 1 cycle of ICI between 2013 and 2019. Patient characteristics, mutation subtype, and ICI outcomes.

Among 48 patients with advanced NSCLC, 14 (29%) had HER2 mutations and 34 (71%) had EGFR mutations. EGFR mutations included 16 (47%) exon 19 deletion, 7 (21%) L858R, 5 (15%) uncommon, and 6 (18%) exon 20 insertion. Compared to EGFR-sensitizing mutations (ESMs), HER2 and EGFR exon 20 mutations were associated with a trend toward better response (respectively, ESM, HER2, and EGFR exon 20 11%, 29%, and 50%; P= .07) and significantly better disease control rates (respectively, 18%, 57%, and 67%; P= .008). Comcond/third-line unselected cohorts. ICIs remain a treatment option for this genomic subgroup, given the absence of approved targeted therapies for these rare mutations.Functional mitral regurgitation (FMR) is a common and complex valve disease, in which severity and risk stratification is still a conundrum. Although risk increases with FMR severity, it is modulated by subjacent left ventricular (LV) disease. The extent of LV remodeling and dysfunction is traditionally evaluated by echocardiography, but a growing body of evidence shows that myocardial fibrosis (MF) assessment by cardiac magnetic resonance (CMR) may complement risk stratification and inform treatment decisions. This review summarizes the current knowledge on the comprehensive evaluation that CMR can provide for patients with FMR, in particular for the assessment of MF and its potential impact in clinical decision-making.
The aims of this study were to 1) develop a formula for projected transmitral gradient (TMG), expected gradient under normal heart rate (HR), and stroke volume (SV); and 2) assess the prognostic value of projected TMG.

In mitral stenosis (MS), TMG is highly dependent on hemodynamics, often leading to discordance between TMG and mitral valve area.

All patients with suspected MS based on echocardiography from 2001 to 2017 were analyzed. Data were randomly split (21); projected TMG was modeled in the derivation cohort, then tested in the validation cohort. The composite endpoint was death or mitral valve intervention.

Of 4,973 patients with suspected MS, severe and moderate MS, defined as mitral valve area≤1.5 and >1.5 to 2.0cm
, were present in 437 (9%) and 936 (19%), respectively. Sorafenib Raf inhibitor In the derivation cohort (n=3,315; age 73 ± 12 years; 34% male), corresponding gradients were TMG≥6 and 4 to<6mmHg, respectively, under normal hemodynamics. Based on the impact of hemodynamics on TMG, the formula was projected TMG=TMG - 0.07 (HR - 70) - 0.03 (SV - 97) in men and projected TMG=TMG - 0.08 (HR - 72) - 0.04 (SV - 84) in women. In the validation cohort (n=1,658), projected TMG had better agreement with MS severity than TMG (kappa 0.61 vs. 0.28). Among 281 patients with TMG≥6mmHg, projected TMG≥6mmHg, present in 171 patients (61%), was associated with higher probability of the endpoint versus projected TMG<6mmHg (adjusted hazard ratio 1.8; 95% confidence interval 1.2 to 2.6; p<0.01).

The novel concept of projected TMG, constructed using the observed impact of HR and SV on TMG, significantly improved the concordance of gradient and valve area in MS and provided better risk stratification than TMG.
The novel concept of projected TMG, constructed using the observed impact of HR and SV on TMG, significantly improved the concordance of gradient and valve area in MS and provided better risk stratification than TMG.
This study sought to assess the impact of right ventricular dysfunction (RVD) as defined by impaired right ventricular-to-pulmonary artery (RV-PA) coupling, on survival after edge-to-edge transcatheter mitral valve repair (TMVR) for severe secondary mitral regurgitation (SMR).

Conflicting data exist regarding the benefit of TMVR in severe SMR. A possible explanation could be differences in RVD.

Using data from the EuroSMR (European Registry on Outcomes in Secondary Mitral Regurgitation) registry, this study compared the characteristics and outcomes of SMR patients undergoing TMVR, according to their RV-PA coupling, assessed by tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure (TAPSE/sPAP) ratio.

Overall, 817 patients with severe SMR and available RV-PA coupling assessment underwent TMVR in the participating centers. RVD was present in 211 patients (25.8% with a TAPSE/sPAP ratio<0.274mm/mmHg). Although all patients demonstrated significant improvement in their New Yorking TMVR procedures for patients with severe SMR.
This study aimed to perform an external validation of the value of right ventricular (RV) deformation patterns and RV mechanical dispersion in patients with arrhythmogenic cardiomyopathy (AC). Secondly, this study assessed the association of these parameters with life-threatening ventricular arrhythmia (VA).

Subtle RV dysfunction assessed by echocardiographic deformation imaging is valuable in AC diagnosis and risk prediction. Two different methods have emerged, the RV deformation pattern recognition and RV mechanical dispersion, but these have neither been externally validated nor compared.

We analyzed AC probands and mutation-positive family members, matched from 2 large European referral centers. We performed speckle tracking echocardiography, whereby we classified the subtricuspid deformation patterns from normal to abnormal and assessed RV mechanical dispersion from 6 segments. We defined VA as sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapy, or abortedrs in AC. Adding RV mechanical dispersion to RV deformation patterns significantly improved the association with life-threatening VA, indicating incremental value.
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