Systematic review of first-in-human and early phase clinical trials for surgically implantable biological mitral valve substitutes.

BACKGROUND: The aim of this review was the creation of uniform protocols to carry out and disclose First-In-Human and preliminary clinical trials of biological mitral valve replacement. The need for consistent methodology in these early trials was highlighted by the observation of significant variability in the methods and protocols used across different research. METHODS: An extensive search through six major databases was carried out to retrieve First-In-Human (FIH) clinical studies evaluating surgically implanted bio-prostheses in the mitral position. RESULTS: Following the PRISMA guideline, a systematic search identified 2082 published articles until March 2023. After removing duplicates (189), 1862 citations were screened, resulting in 22 eligible studies with 3332 patients for analysis. The mitral valve prostheses in these studies ranged from 21 to 37 mm, with the 29 mm size being most prevalent. Patient numbers varied, with the FIH subgroup including 31 patients and the older subgroup including 163 patients. Average study durations differed: the older subgroup lasted 4.57 years, the FIH subgroup 2.85 years, and the early phase studies spanned 8.05 years on average. CONCLUSION: FIH clinical report is essential to assess the significance of clinical data required for a "de novo" surgical implant. In addition, understanding the performance of the device, and recognizing the difficulties associated with the innovation constitute important lessons. These insights could be beneficial for the development of bioprosthetic heart valves and formulating a protocol for an FIH clinical trial.

Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.

Anaesthesia for Angelman syndrome.

We describe the administration of anaesthesia to a patient with Angelman syndrome, which is characterised by an abnormality of chromosome 15, where a subunit of the GABA receptor is coded. This has far-reaching anaesthetic implications as many drugs used in anaesthesia are thought to act via GABA receptors. Our patient had an uneventful peri-operative period and was discharged home on the second postoperative day.