PDF - 35KB, Supplemental Table showing IC50s of chemotherapy, BIBF 1120 and tbe combination in lung and pancreatic cancer cell lines.

PDF - 31KB, Supplemental table of antibodies.

PDF - 118KB, Immunohistochemical evaluation and quantification of phospho-histone H3, Ki67, and cleaved caspase 3 in A549 and MIA PaCa-2 xenografts.

PDF - 117KB, Supplemental data showing the activity of BIBF 1120 as a single agent in A549 xenografts.

Despite the remarkable success of immune checkpoint inhibitor (ICI) therapy, a significant number of patients develop severe and unpredictable immune-related adverse events (irAEs) affecting a wide variety of organs. Concerns over irAE have led to the exclusion of patients with autoimmune disease from ICI clinical trials. Role of host genetic and immune factors in mediating irAEs remain unclear and it is not clear if the manifestations of irAEs is associated with response to therapy. Here, we use multi-faceted approach to characterize changes in host immune system in 200 patients receiving ICI therapy at baseline and post immunotherapy. In addition, we assessed genetic predisposition to autoimmunity using the Illumina SNP array and via targeted resequencing of over 150 immunoregulatory loci including the HLA region. In this meeting, we will present our initial genetic data, serum cytokine and autoantibody profiles and RNA sequencing on peripheral blood mononuclear cells (PBMCs) at baseline and post immunotherapy in patients with and without irAEs. Our preliminary findings suggest that patients who developed irAEs have lower baseline levels and greater post-treatment increases in key interferon gamma inducible cytokine/chemokine levels. Our autoantibody profiling data reveals unique sets of autoantibodies associated with specific irAEs. We will present a comprehensive analysis of immune and genetic correlates of irAEs and response to therapy. We hope our study can help gain insight in to the mechanisms underlying irAE and to identify biomarker signatures predictive of irAEs and/or response. These findings may ultimately help identify high-risk patients, customize therapy, expand use of immunotherapy and prevent toxicities.

BACKGROUND: Flow cytometric crossmatching is currently the method of choice for most transplantation programs before kidney transplantation. In July of 2017, our program implemented the virtual crossmatch, without a prospective physical crossmatch, for the majority of patients in the setting of a new kidney allocation system implemented by the United Network for Organ Sharing. STUDY DESIGN: A retrospective review was conducted to determine whether virtual crossmatching could reduce cold ischemia time (CIT). Secondary outcomes included the incidence of delayed graft function and 1-year patient and allograft failure. RESULTS: A total of 825 patients received a kidney transplant between December 1, 2014 and July 1, 2018; 505 were in the pre-implementation group and 227 were in the post-implementation group. The CIT decreased between the pre-implementation era to post implementation era from 16.67 +/- 8.7 hours to 14.5 +/- 8.2 hours (p = 0.002). On univariate analysis, delayed graft function (DGF) rates were similar between the 2 eras (19% vs 17%; p = 0.415), despite having more donations after cardiac death and higher Kidney Donor Profile Index donors in the post-implementation era. There was no difference in biopsy-proven acute rejection (n = 28 [5.6%] vs n = 8 [3.5%]; p = 0.226), 1-year graft loss (4% vs 3%; p = 0.304), or patient death (2% vs 1%; p = 0.567) rate between groups. On multivariable modeling for mean CIT and incidence of DGF, patients receiving transplants in the post-implementation era had an adjusted reduction in CIT of an estimated 2.35 hours (95% CI, 1.15 to 3.55; p < 0.001). Patients in the post-implementation era also had 26% lower odds of DGF developing (odds ratio 0.74; 95% CI, 0.48 to 1.14; p = 0.170), after adjusting for covariates. CONCLUSIONS: Kidney transplantation can be safely performed with virtual crossmatching, without a prospective physical crossmatch with improved CIT and potentially reduced DGF rate without increased risk of rejection. ((C) 2020 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

A discussion of the ethical and medical considerations of pregnancy for women who have undergone organ transplantation. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

This case represents a rare association of Ellis-van Creveld (EvC) syndrome, a chondroectodermal disorder, with congenital paucity of bile ducts. Sequential liver biopsies during the patient's childhood demonstrated progressive fibrosis that can occur in other chondrodysplastic malformations. However, this EvC case is the first report to demonstrate paucity of intra-hepatic bile ducts progressing to cirrhosis and subsequently requiring transplant.