Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure.

BACKGROUND & AIMS: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86), is a negative regulator of T-cell activation. We collected T cells from patients with ALF and investigated whether inhibitory signals down-regulate adaptive immune responses in patients with ALF. METHODS: We collected peripheral blood mononuclear cells from patients with ALF and controls from September 2013 through September 2015 (45 patients with ALF, 20 patients with acute-on-chronic liver failure, 15 patients with cirrhosis with no evidence of acute decompensation, 20 patients with septic shock but no cirrhosis or liver disease, and 20 healthy individuals). Circulating CD4+ T cells were isolated and analyzed by flow cytometry. CD4+ T cells were incubated with antigen, or agonist to CD3 and dendritic cells, with or without antibody against CTLA4; T-cell proliferation and protein expression were quantified. We measured levels of soluble B7 molecules in supernatants of isolated primary hepatocytes, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood samples from patients with ALF had a higher proportion of CD4+ CTLA4+ T cells than controls; patients with infections had the highest proportions. CD4+ T cells from patients with ALF had a reduced proliferative response to antigen or CD3 stimulation compared to cells from controls; incubation of CD4+ T cells from patients with ALF with an antibody against CTLA4 increased their proliferative response to antigen and to CD3 stimulation, to the same levels as cells from controls. CD4+ T cells from controls up-regulated expression of CTLA4 after 24-48 hours culture with sera from patients with ALF; these sera were found to have increased concentrations of soluble B7 compared to sera from controls. Necrotic human primary hepatocytes exposed to acetaminophen, but not hepatic sinusoidal endothelial cells and biliary epithelial cells from patients with ALF, secreted high levels of soluble B7. Sera from mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+ T cells from patients with ALF have increased expression of CTLA4 compared to individuals without ALF; these cells have a reduced response to antigen and CD3 stimulation. We found sera of patients with ALF and from mice with liver injury to have high concentrations of soluble B7, which up-regulates CTLA4 expression by T cells and reduces their response to antigen. Plasma exchange reduces levels of B7 in sera from patients with ALF and might be used to restore antimicrobial responses to patients

Enquête sur la pratique de la téléconsultation médicale en oncologie en Auvergne Rhône Alpes

International audienc

A qualitative study of teleconsultation practices among French oncologists in a post-COVID-19 period

Background The Covid-19 pandemic has prompted healthcare professionals to adapt and implement new tools to ensure continuity of patient care. Teleconsultation became the only option for some practitioners who had never used it previously and boosted its use for others who already used it. Several studies have reviewed the use of teleconsultation in oncology during the epidemic, but few have addressed its continued use and how practitioners view it in a post-epidemic period. The aim of this survey was to conduct a qualitative exploration of how oncologists use teleconsultation in their daily practice in a post-COVID 19 period. Materials and Methods For this qualitative study, semi-structured interviews were conducted with oncologists in France who utilized teleconsultation in the field of oncology during the COVID-19 period. The interview guide included questions on the interests and limitations of using teleconsultation in oncology, on reluctance to use it among oncologists, and invited participants to formulate proposals for more optimal use. Results Fourteen oncologists participated in the survey. Currently, 12% of the consultations of the surveyed practitioners are conducted via teleconsultation. Seven themes were identified in the analysis of the interviews: (a) The oncologist and teleconsultation; (b) Clinical motivations for using teleconsultation; (c) Comparison between teleconsultation and in-person consultation; (d) Advantages and disadvantages of teleconsultation; (e) Technical modalities of teleconsultation; (f) Role of Covid and confinement in the use of teleconsultation; (h) Epistemic judgments about teleconsultation. Optimal teleconsultation occurs when seamlessly incorporated into patient care, offering reduced patient inconvenience, and providing economic and environmental benefits. Although there's a lack of unified agreement in research literature regarding time efficiency, teleconsultation facilitates more customized patient monitoring and addresses the challenge of “medical deserts” nationally. Considering patient preferences is crucial when contemplating the use of teleconsultation. Predominantly, technical issues stand as the principal barriers to teleconsultation implementation. Conclusion Even after the end of the health crisis, teleconsultation is still used in clinical practice. Recommendations for effective use are suggested

Enquête sur la pratique de la téléconsultation médicale en oncologie en Auvergne Rhône Alpes

International audienc