Three patients with the rare anomaly of congenital absence of the ostium of the left main coronary artery are presented. In two of the patients, aged 50 and 52 respectively, the diagnosis was established during selective coronary cineangiography for a severe anginal syndrome. The third patient, a 16-year-old-girl, underwent cardiac catheterization for investigation of a congenital heart malformation, when a single right coronary artery was demonstrated with absence of the main coronary artery ostium. Two patients underwent successful aortocoronary bypass grafting. In view of the occurrence of sudden death and massive myocardial infarction in adult patients shown to have severe or complete obstruction of the left main coronary artery, it is suggested that adult patients with this condition, who require open-heart surgery for any other cardiac disorder, should undergo aortocoronary bypass grafting concurrently even prior to the development of anginal symptoms. Children shown to have this anomaly should be subjected to long-term follow-up and have an aortocoronary bypass graft performed when symptoms of coronary insufficiency develop.
Background: Temporary disruption of the blood-brain barrier (BBB) using pulsed ultrasound leads to the clearance of both amyloid and tau from the brain, increased neurogenesis, and mitigation of cognitive decline in pre-clinical models of Alzheimer’s disease (AD) while also increasing BBB penetration of therapeutic antibodies. The goal of this pilot clinical trial was to investigate the safety and the efficacy of this approach in patients with mild AD using an implantable ultrasound device.Methods: An implantable, 1 MHz ultrasound device (SonoCloud-1) was extradurally implanted under local anesthesia in the skull of 10 mild AD patients to target the left supra-marginal gyrus. Over 3.5 months, seven ultrasound sessions in combination with intravenous infusion of microbubbles were performed twice per month to temporarily disrupt the BBB. 18F-Florbetapir and 18F-fluorodeoxyglucose positron emission tomography (PET) imaging were performed on a combined PET/MRI scanner at inclusion and at four and eight months after initiation of sonications to monitor brain metabolism and amyloid levels along with cognitive evaluations. Evolution of cognitive and neuroimaging features were compared to that of a matched sample of control participants.Results: A total of 63 BBB opening procedures were performed in nine subjects. The procedure was well-tolerated. A non-significant decrease in amyloid accumulation at four months of -6.6% (SD=7.2%) on 18F-Florbetapir PET imaging in the sonicated gray matter targeted by the ultrasound transducer was observed compared to baseline in six subjects that completed treatments and who had evaluable imaging scans. No differences in longitudinal change in glucose metabolism were observed compared to neighboring or contralateral regions or to the change observed in the same region in ADNI participants. No significant effect on cognition evolution was observed in comparison to the ADNI participants as expected due to the small sample size and duration of the trial.Conclusions: These results demonstrate the safety of ultrasound-based BBB disruption and potential of this technology to be used as a therapy for AD patients. They support further research of this technique in a larger clinical trial with a device designed to sonicate larger volumes of tissue and in combination with disease modifying drugs to further enhance the effects observed. Trial registration: NCT03119961 (clinicaltrials.gov)
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