Transapical off-pump mitral valve repair with Neochord Implantation (TOP-MINI): step-by-step guide

open10openColli, Andrea; Zucchetta, Fabio; Torregrossa, Gianluca; Manzan, Erica; Bizzotto, Eleonora; Besola, Laura; Bellu, Roberto; Sarais, Cristiano; Pittarello, Demetrio; Gerosa, GinoColli, Andrea; Zucchetta, Fabio; Torregrossa, Gianluca; Manzan, Erica; Bizzotto, Eleonora; Besola, Laura; Bellu, Roberto; Sarais, Cristiano; Pittarello, Demetrio; Gerosa, Gin

Single-cell genotyping and transcriptomic proling in focal cortical dysplasia

Focal cortical dysplasia type II (FCDII) is a cortical malformation causing refractory epilepsy. FCDII arises from developmental somatic mutations in mTOR pathway genes, leading to focal cortical dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic mutations and how they affect cell-type-specific transcriptional programs remains unknown. To address this question, here we combined single-nucleus genotyping and transcriptomics in morphologically-identified cells using surgical cortical samples from genetically-characterized FCDII patients. Mutations were predominantly detected in glutamatergic neurons and astrocytes and only a small fraction of mutated cells exhibited cytomegalic features, revealing incomplete penetrance of FCDII-causing mutations. Moreover, we identified cell-type-specific transcriptional dysregulations in both mutated and non-mutated FCDII cells, including synapse and neurodevelopment-related pathways, that may account for epilepsy, and dysregulation of mitochondrial metabolism pathways in cytomegalic cells. Together, these findings reveal cell-autonomous and non-cell-autonomous mechanisms at play in FCDII, towards the development of precision therapies for this disorder

Risk stratification of severe aortic stenosis according to new guidelines: Long term outcomes

Background: Current ESC and ACC/AHA guidelines for the management of valvular heart disease assign a class Ia indication for aortic valve replacement (AVR) only to patients with symptomatic severe aortic valve stenosis and asymptomatic patients with depressed left ventricular ejection fraction (LVEF <50%) or positive exercise test. We examined the long-term outcomes for patients undergoing AVR for aortic stenosis over a 11-year period at our institution compared to current international guidelines for AVR. Methods: Patients who had undergone isolated AVR for severe aortic valve stenosis between January 2001 and December 2012 were selected. The population was divided into subgroups based on preoperative LVEF (< or 6550%) and on presence/absence of symptoms (NYHA =I or 65II, respectively). Results: We identified 607 patients with a median follow-up (FU) time of 5.75 years (IQR 3.24\u20138.00 years). The presence of symptoms did not have a significant impact on cardiovascular mortality (P=0.201). Patients with LVEF <50% displayed a higher long-term cardiovascular mortality rate (P=0.015). Multivariate analysis showed that preserved LVEF was a protective factor for asymptomatic patients (P=0.021), while preoperative LVEF did not affect the mortality rate in symptomatic patients (HR 0.88; 95% CI, 0.54\u20131.44). Correspondingly, asymptomatic patients with reduced LVEF were found to be at a higher risk of long-term mortality compared to the other groups (P=0.011). The only other independent risk factor for death was age (HR 6.46; 95% CI, 2.22\u201318.76). Conclusions: According to our data, current international class I indications for symptomatic patients ensure good long-term survival, while class I indications for asymptomatic patients with reduced LVEF are associated with poor long-term survival. Our results suggest that early surgery should also be considered also for asymptomatic patients with preserved LVEF, particularly in cases of very low operative risk. \ua9 Journal of Thoracic Disease. All rights reserved