Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting

International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...     

Sarcopenia in cirrhosis: from pathogenesis to interventions

Journal of Gastroenterology - Sarcopenia (severe muscle depletion) is a prevalent muscle abnormality in patients with cirrhosis that confers poor prognosis both pre- and post-liver transplantation....     

Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Detection and measurement of a cellular immune-reactivity towards polyester and polytetrafluoroethylene grafts. Leukocyte adherence inhibition test

Several studies were performed on polyester (Dacron) and polytetrafluoroethylene (PTFE) vascular substitute thrombogenicity. However, to date, the host-graft interactions have yet to be studied from an immunological point of view. For this reason, 4 classes of 10 patients each (Class 1: Dacron-+PTFE-grafted patients, Class 2: Dacron-, Class 3: PTFE-, and Class 4: controls) were submitted to a cellular immune-reactivity test: leukocyte adherence inhibition (LAI), in which leukocytes fail to adhere to glass on contact with a sensitizing antigen. The following blood cell populations were used: total leukocytes (PBL), mononuclear cells (MNC), T and B lymphocytes. This research demonstrated that a T cellular immune-reactivity towards Dacron and PTFE respectively occurs in Dacron- and PTFE-grafted patients, and that this reactivity is greater in the case of Dacron. More studies are required to determine the immuno-competent system role in fabric prosthesis patency.