Survey of the Impact of COVID-19 on Chronic Liver Disease Patient Care Experiences and Outcomes.

Background: The COVID-19 pandemic has a secondary impact on the health of patients with chronic liver disease (CLD). Our objective was to study this impact on care provision, telemedicine, and health behaviours in CLD patients. Methods: CLD patients of an urban gastroenterology clinic who attended a telemedicine appointment between March 17, 2020 and September 17, 2020, completed an online survey on care delays, health behaviours, and experience with telemedicine. Chart review was conducted in 400 randomly selected patients: 200 charts from during the pandemic were compared to 200 charts the previous year. Data were extracted for clinicodemographic variables, laboratory investigations, and clinical outcomes. Results: Of 399 patients invited to participate, 135 (34%) completed the online survey. Fifty (39%) patients reported 83 care delays due to the COVID-19 pandemic, with the majority (71%) of delays persisting beyond 2 months. Ninety-five (75%) patients were satisfied with telemedicine appointments. There was a longer delay between lab work and appointments in patients seen during the pandemic compared to 2019 (P = 0.01). Compared to the year prior, during the COVID pandemic, there was a similar number of cases of cirrhosis decompensation (n = 26, 13% versus n = 22, 11%) and hospitalization (n = 12, 6% versus n = 5, 3%). Conclusion: The COVID-19 pandemic has led to care delays for CLD outpatients, with most delays on the scale of months. These patient-reported experiences and clinical observations can direct optimization of CLD care as effects from the pandemic evolve.

Liver Transplant Recipients Speak Out on Public Awareness and Education Surrounding Alcohol-Related Health Effects: A Survey Study.

BACKGROUND: Compared to other recreational substances in Canada, alcohol consumption incurs the highest healthcare costs. Liver transplant recipients are unique stakeholders as members of the general public with lived experiences of liver disease. We sought to explore their perspectives on the current state of public education on alcohol-related health effects. METHODS: The most recent 400 liver transplant recipients at Vancouver General Hospital, Canada, were invited to participate in an anonymous online survey on alcohol-related health effects by mail, email, and phone. RESULTS: Of 372 contacted patients, 212 (57%) completed the survey. Most patients were between 60-79 years, 63% were male, and 69% were Caucasian. The most common liver conditions leading to transplant were viral hepatitis (33%), alcohol-related liver disease (16%), autoimmune liver disease (14%), and non-alcoholic fatty liver disease (15%). Most patients knew that alcohol leads to liver failure (85%), but fewer knew about alcohol leading to cancer (54%), heart disease (50%), and damage to other organs (58%). Most common sources of information included public media (61%), family and friends (52%), and physicians (49%), with narrative comments about learning of alcohol-related health effects after liver diagnosis. Most patients believed that public health education at a middle/high school level would have long-term efficacy (72%) compared to health warning labels (33%) and safety messaging in commercials (39%). Current public education was felt to be adequate by only 20% of patients and 73% of patients supported health warning labels. CONCLUSIONS: Liver transplant patients reported a high, but not universal, awareness of alcohol-related health effects. A majority thought that current public health efforts were inadequate; it is critical to implement public health interventions to ensure consumers are able to make an informed decision on alcohol consumption.

Müller cell degeneration and microglial dysfunction in the Alzheimer's retina.

Amyloid beta (Aß) deposits in the retina of the Alzheimer's disease (AD) eye may provide a useful diagnostic biomarker for AD. This study focused on the relationship of Aß with macroglia and microglia, as these glial cells are hypothesized to play important roles in homeostasis and clearance of Aß in the AD retina. Significantly higher Aß load was found in AD compared to controls, and specifically in the mid-peripheral region. AD retina showed significantly less immunoreactivity against glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) compared to control eyes. Immunoreactivity against ionized calcium binding adapter molecule-1 (IBA-1), a microglial marker, demonstrated a higher level of microgliosis in AD compared to control retina. Within AD retina, more IBA-1 immunoreactivity was present in the mid-peripheral retina, which contained more Aß than the central AD retina. GFAP co-localized rarely with Aß, while IBA-1 co-localized with Aß in more layers of control than AD donor retina. These results suggest that dysfunction of the Müller and microglial cells may be key features of the AD retina.

Fluorescent Isoindole Crosslink (FlICk) Chemistry: A Rapid, User-friendly Stapling Reaction.

The stabilization of peptide secondary structure via stapling is a ubiquitous goal for creating new probes, imaging agents, and drugs. Inspired by indole-derived crosslinks found in natural peptide toxins, we employed ortho-phthalaldehydes to create isoindole staples, thus transforming inactive linear and monocyclic precursors into bioactive monocyclic and bicyclic products. Mild, metal-free conditions give an array of macrocyclic α-melanocyte-stimulating hormone (α-MSH) derivatives, of which several isoindole-stapled α-MSH analogues (Ki ≈1 nm) are found to be as potent as α-MSH. Analogously, late-stage intra-annular isoindole stapling furnished a bicyclic peptide mimic of α-amanitin that is cytotoxic to CHO cells (IC50 =70 µm). Given its user-friendliness, we have termed this approach FlICk (fluorescent isoindole crosslink) chemistry.