Perioperative Complications and Long-Term Follow-Up of Liver Transplantation in Hemorrhagic Hereditary Telangiectasia: Report of Three Cases and Systematic Review

The aim was to describe three patients with hemorrhagic hereditary telangiectasia (HHT) requiring liver transplantation (LT) and to perform a systematic review focusing on surgical complications and long-term follow-up. Unrestricted searches of the Medline and Embase databases were performed through February 2022. Forty-five studies were selected including 80 patients plus the three new reported patients, 68 (81.9%) were female and mean age was 50 (27-72) years. Main indications for LT were high-output cardiac failure (n = 40; 48.2%), ischemic cholangitis (n = 19; 22.9%), and a combination of both conditions (n = 13;15.6%). Mean cold ischemic time and red blood cell units transfused during LT were 554 (300-941) minutes and 11.4 (0-88) units, respectively. Complications within 30 days were described in 28 (33.7%) patients, mainly bleeding complications in 13 patients, hepatic artery (HA) thrombosis in four and hepatic vein thrombosis in one. Mean follow-up was 76.4 (1-288) months, and during it, four new patients developed thrombotic complications in HA, HA aneurysm, celiac artery, and the portal-splenic-mesenteric vein. HHT relapse in the transplant allograft was detected in 13 (17.1%) patients after 1-19 years (including two fatal recurrences). Overall mortality was 12%. In conclusion, previous assessment of HA anatomy and hyperdynamic circulatory state could reduce LT complications. The risk of relapse in the hepatic graft supports a multidisciplinary follow-up for HHT patients with LT

VPS13A knockdown impairs corticostriatal synaptic plasticity and locomotor behavior in a new mouse model of chorea-acanthocytosis

Chorea-acanthocytosis (ChAc) is an inherited neurodegenerative movement disorder caused by VPS13A gene mutations leading to the absence of protein expression. The striatum is the most affected brain region in ChAc patients. However, the study of the VPS13A function in the brain has been poorly addressed. Here we generated a VPS13A knockdown (KD) model and aimed to elucidate the contribution of VPS13A to synaptic plasticity and neuronal communication in the corticostriatal circuit. First, we infected primary cortical neurons with miR30-shRNA against VPS13A and analyzed its effects on neuronal plasticity. VPS13A-KD neurons showed a higher degree of branching than controls, accompanied by decreased BDNF and PSD-95 levels, indicative of synaptic alterations. We then injected AAV-KD bilaterally in the frontal cortex and two different regions of the striatum of mice and analyzed the effects of VPS13A-KD on animal behavior and synaptic plasticity. VPS13A-KD mice showed modification of the locomotor behavior pattern, with increased exploratory behavior and hyperlocomotion. Corticostriatal dysfunction in VPS13A-KD mice was evidenced by impaired striatal long-term depression (LTD) after stimulation of cortical afferents, which was partially recovered by BDNF administration. VPS13A-KD did not lead to neuronal loss in the cortex or the striatum but induced a decrease in the neuronal release of CX3CL1 and triggered a microglial reaction, especially in the striatum. Notably, CX3CL1 administration partially restored the impaired corticostriatal LTD in VPS13A-KD mice. Our results unveil the involvement of VPS13A in neuronal connectivity modifying BDNF and CX3CL1 release. Moreover, the involvement of VPS13A in synaptic plasticity and motor behavior provides key information to further understand not only ChAc pathophysiology but also other neurological disorders

Information Asymmetry in Hospitals: Evidence of the Lack of Cost Awareness in Clinicians

Background: Information asymmetries and the agency relationship are two defining features of the healthcare system. These market failures are often used as a rationale for government intervention. Many countries have government financing and provision of healthcare in order to correct for this, while health technology agencies also exist to improve efficiency. However, informational asymmetries and the resulting principal-agent problem still persist, and one example is the lack of cost awareness amongst clinicians. This study explores the cost awareness of clinicians across different settings. / Methods: We targeted four clinical cohorts: medical students, Senior House Officers/Interns, Mid-grade Senior Registrar/Residents, and Consultant/Attending Physicians, in six hospitals in the United Kingdom, the United States, Australia, New Zealand and Spain. The survey asked respondents to report the cost (as they recalled) of different types of scans, visits, medications and tests. Our analysis focused on the differential between the perceived/recalled cost and the actual cost. We explored variation across speciality, country and other potential confounders. Cost-awareness levels were estimated based on the cost estimates within 25% of the actual cost. / Results: We received 705 complete responses from six sites across five countries. Our analysis found that respondents often overestimated the cost of common tests while underestimating high-cost tests. The mean cost-awareness levels varied between 4 and 23% for different items. Respondents acknowledged that they did not feel they had received adequate training in cost awareness. / Discussion: The current financial climate means that cost awareness and the appropriate use of scarce healthcare resources is more paramount than perhaps ever before. Much of the focus of health economics research is on high-cost innovative technologies, yet there is considerable waste in the system with respect to overtreatment and overdiagnosis. Common reasons put forward for this include defensive medicine, poor education, clinical uncertainty and the institution of protocols. / Conclusion: Given the role of clinicians in the healthcare system, as agents both for patients and for providers, more needs to be done to remove informational asymmetries and improve clinician cost awareness