Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma.

BACKGROUND: It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis. METHODS: Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes. RESULTS: 47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 â€‹%,p â€‹= â€‹0.001) and less likely to survive(16%vs56 â€‹%,p â€‹= â€‹0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32-10.25],HR survival:3.80[1.38-10.46]). CONCLUSIONS: TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.

Combined islet and kidney xenotransplantation for diabetic nephropathy: an update in ongoing research for a clinically relevant application of porcine islet transplantation.

Combined islet and kidney xenotransplantation for the treatment of diabetic nephropathy represents a compelling and increasingly relevant therapeutic possibility for an ever-growing number of patients who would benefit from both durable renal replacement and cure of the underlying cause of their renal insufficiency: diabetes. Here we briefly review immune barriers to islet transplantation, highlight preclinical progress in the field, and summarize our experience with combined islet and kidney xenotransplantation, including both challenges with islet-kidney composite grafts as well as our recent success with sequential kidney followed by islet xenotransplantation in a pig-to-baboon model.

A clinical coagulopathy score concurrent with viscoelastic testing defines opportunities to improve hemostatic resuscitation and enhance blood product utilization during liver transplantation.

BACKGROUND: An NIH clinical coagulopathy score has been devised for trauma patients, but no such clinical score exists in transplantation surgery. We hypothesize that that this coagulopathy score can effectively identify laboratory defined coagulopathy during liver transplantation and correlates to blood product utilization. METHODS: TEGs were performed and coagulopathy scores (1, normal bleeding - 5, diffuse coagulopathic bleeding) were assigned by the surgeons at 5 intra-operative time points. Blood products used during the case were recorded between time points. Statistical analyses were performed to identify correlations between coagulopathy scores, TEG-detected abnormalities, and blood product utilization. RESULT: Transfusions rarely correlated with the appropriate TEG measurements of coagulation dysfunction. Coagulopathy score had significant correlation to various transfusions and TEG-detected coagulopathies at multiple points during the case. High aggregate coagulopathy scores identified patients receiving more transfusions, re-operations, and longer hospital stays CONCLUSION: The combination of viscoelastic testing and a standardized clinical coagulopathy score has the potential to optimize transfusions if used in tandem as well as standardize communication between surgery and anesthesia teams about clinically evident coagulopathy.

The use of thromboelastography to assess post-operative changes in coagulation and predict graft function in renal transplantation.

BACKGROUND: End stage renal disease (ESRD) is associated with elevated fibrinogen levels and fibrinolysis inhibition. However, there is a paucity of data on how renal transplantation impacts coagulation. we hypothesize that renal transplantation recipients with good functioning grafts will have improved fibrinolytic activity following surgery. METHODS: Kidney recipients were analyzed pre-operatively and on post-operative day 1(POD1) using three different TEG assays with and without two concentration of tissue-plasminogen activator (t-PA). TEG indices and percent reduction in creatinine from pre-op to POD1 were measured, with >50% defining "good" graft function. Follow up was done at 6, 12, and 24 months. RESULTS: Percent lysis(LY30) on POD1 the t-PA TEG was significantly correlated to change creatinine from pre-op to POD-1(p = 0.006). A LY30 ≥ 23% was associated with good early graft function, and lower creatinine at 24-months(p = 0.028) compared to recipients with low POD1 LY30. CONCLUSIONS: Post-operative tPA-TEG LY30 is associated with favorable early and late outcomes in kidney transplant.

Identification of CD112R as a novel checkpoint for human T cells.

T cell immunoglobulin and ITIM domain (TIGIT) and CD226 emerge as a novel T cell cosignaling pathway in which CD226 and TIGIT serve as costimulatory and coinhibitory receptors, respectively, for the ligands CD155 and CD112. In this study, we describe CD112R, a member of poliovirus receptor-like proteins, as a new coinhibitory receptor for human T cells. CD112R is preferentially expressed on T cells and inhibits T cell receptor-mediated signals. We further identify that CD112, widely expressed on antigen-presenting cells and tumor cells, is the ligand for CD112R with high affinity. CD112R competes with CD226 to bind to CD112. Disrupting the CD112R-CD112 interaction enhances human T cell response. Our experiments identify CD112R as a novel checkpoint for human T cells via interaction with CD112.