RESUMEN
OBJECTIVE: Many patients undergoing thoracoabdominal aortic aneurysm (TAAA) repair have had a previous myocardial infarction (MI). To address the paucity of data regarding outcomes in such patients, we aimed to compare outcomes after open TAAA repair in patients with and without previous MI. METHODS: From 1986 to 2022, we performed 3737 consecutive open TAAA repairs. Of these, 706 (18.9%) were in patients with previous MI. We used multivariable logistic regression to identify predictors of operative death. Propensity score matching analyzed preoperative and select operative variables to create matched groups of patients with or without a previous MI (n = 704 pairs). Late survival was determined by Kaplan-Meier analysis and compared by log rank test. RESULTS: Overall, operative mortality was 8.5% and the adverse event rate was 15.2%; these were elevated in patients with MI (11.0% vs 7.9% [P = .01] and 18.0% vs 14.6% [P = .02], respectively). In the propensity score-matching cohort, the MI group had a greater rate of cardiac complications (32.4% vs 25.4%; P = .005) and delayed paraparesis (5.1% vs 2.4%; P = .1); however, there was no difference in operative mortality (11.1% vs 10.9%; P = 1) or adverse event rate (18.0% vs 16.8%; P = .6). Overall, previous MI was not independently associated with operative mortality in multivariable analysis (P = .1). The matched MI group trended toward poorer 10-year survival (29.8% ± 1.9% non-MI vs 25.0% ± 1.8% MI; P = .051). CONCLUSIONS: Although previous MI was not associated with early mortality after TAAA repair, patients with a previous MI had greater rates of cardiac complications and delayed paraparesis. Patients with a previous MI also trended toward poorer survival.
RESUMEN
UBE3A encodes ubiquitin protein ligase E3A, and in neurons its expression from the paternal allele is repressed by the UBE3A antisense transcript (UBE3A-ATS). This leaves neurons susceptible to loss-of-function of maternal UBE3A. Indeed, Angelman syndrome, a severe neurodevelopmental disorder, is caused by maternal UBE3A deficiency. A promising therapeutic approach to treating Angelman syndrome is to reactivate the intact paternal UBE3A by suppressing UBE3A-ATS. Prior studies show that many neurological phenotypes of maternal Ube3a knockout mice can only be rescued by reinstating Ube3a expression in early development, indicating a restricted therapeutic window for Angelman syndrome. Here, we report that reducing Ube3a-ATS by antisense oligonucleotides in juvenile or adult maternal Ube3a knockout mice rescues the abnormal electroencephalogram (EEG) rhythms and sleep disturbance, two prominent clinical features of Angelman syndrome. Importantly, the degree of phenotypic improvement correlates with the increase of Ube3a protein levels. These results indicate that the therapeutic window of genetic therapies for Angelman syndrome is broader than previously thought, and EEG power spectrum and sleep architecture should be used to evaluate the clinical efficacy of therapies.
