Implementation of a Bleeding Management Algorithm in Liver Transplantation: A Pilot Study.

Objectives: The aims of the study were to compare the consumption of blood products before and after the implementation of a bleeding management algorithm in patients undergoing liver transplantation and to determine the feasibility of a multicentre, randomized study. Background: Liver transplantation remains the only curative therapy for patients with end-stage liver disease, but it carries a high risk of surgical bleeding. Materials and Methods: Retrospective study of patients treated before (group 1) and after (group 2) implementation of a haemostatic algorithm guided by viscoelastic testing, including use of lyophilized coagulation factor concentrates (prothrombin complex and fibrinogen concentrates). Primary outcome was the number of units of blood products transfused in 24 h after surgery. Secondary outcomes included hospital stay, mortality, and cost. Results: Data from 30 consecutive patients was analysed; 14 in group 1 and 16 in group 2. Baseline data were similar between groups. Median total blood product consumption 24 h after surgery was 33 U (IQR: 11-57) in group 1 and 1.5 (0-23.5) in group 2 (p = 0.028). Significantly fewer units of red blood cells, fresh frozen plasma, and cryoprecipitate were transfused in group 2 versus group 1. There was no significant difference in complications, hospital stay, or in-hospital mortality between groups. The cost of haemostatic therapy was non-significantly lower in group 2 versus group 1 (7,400 vs. 15,500 USD; p = 0.454). Conclusion: The haemostatic management algorithm was associated with a significant reduction in blood product use during 24 h after liver transplantation. This study demonstrated the feasibility and provided a sample size calculation for a larger, randomized study.

Identifying Factors Predicting Kidney Graft Survival in Chile Using Elastic-Net-Regularized Cox's Regression.

Background and Objectives: We developed a predictive statistical model to identify donor-recipient characteristics related to kidney graft survival in the Chilean population. Given the large number of potential predictors relative to the sample size, we implemented an automated variable selection mechanism that could be revised in future studies as more national data is collected. Materials and Methods: A retrospective multicenter study was conducted to analyze data from 822 adult kidney transplant recipients from adult donors between 1998 and 2018. To the best of our knowledge, this is the largest kidney transplant database to date in Chile. A procedure based on a cross-validated regularized Cox regression using the Elastic Net penalty was applied to objectively identify predictors of death-censored graft failure. Hazard ratios were estimated by adjusting a multivariate Cox regression with the selected predictors. Results: Seven variables were associated with the risk of death-censored graft failure; four from the donor: age (HR = 1.02, 95% CI: 1.00-1.03), male sex (HR = 0.64, 95% CI: 0.46-0.90), history of hypertension (HR = 1.49, 95% CI: 0.98-2.28), and history of diabetes (HR = 2.04, 95% CI: 0.97-4.29); two from the recipient: years on dialysis log-transformation (HR = 1.29, 95% CI: 0.99-1.67) and history of previous solid organ transplantation (HR = 2.02, 95% CI: 1.18-3.47); and one from the transplant: number of HLA mismatches (HR = 1.13, 95% CI: 0.99-1.28). Only the latter is considered for patient prioritization in deceased kidney allocation in Chile. Conclusions: A risk model for kidney graft failure was developed and trained for the Chilean population, providing objective criteria which can be used to improve efficiency in deceased kidney allocation.

Thoracic and diaphragmatic endometriosis: Single-institution experience using novel, broadened diagnostic criteria

Objective: To describe our experience with the multidisciplinary management of both thoracic/diaphragmatic endometriosis (TED), applying a broadened definition of the "Thoracic endometriosis syndrome (TES)" to define cases. Material and Methods: We present a retrospective series of consecutive patients affected by pathology-proven TED, treated at our institution, during a period of 7 years. Results: Five women were included. Two patients were referred due to catamenial chest/shoulder pain, one due to recurrent catamenial pneumothorax, and one due to new-onset diaphragmatic hernia. One patient had no thoracic symptoms, but diaphragmatic endometriosis was found during gynecologic laparoscopy for pelvic endometriosis. Endometriosis was histologically confirmed in all cases. After follow-up, all patients remain asymptomatic. Conclusion: Broadened TES criteria could increase the incidence of TED and determine better knowledge of this condition. Multidisciplinary, minimally invasive surgery is effective and safe, but should be reserved for tertiary referral centers.

Chaperone-mediated autophagy is required for tumor growth.

The cellular process of autophagy (literally "self-eating") is important for maintaining the homeostasis and bioenergetics of mammalian cells. Two of the best-studied mechanisms of autophagy are macroautophagy and chaperone-mediated autophagy (CMA). Changes in macroautophagy activity have been described in cancer cells and in solid tumors, and inhibition of macroautophagy promotes tumorigenesis. Because normal cells respond to inhibition of macroautophagy by up-regulation of the CMA pathway, we aimed to characterize the CMA status in different cancer cells and to determine the contribution of changes in CMA to tumorigenesis. Here, we show consistent up-regulation of CMA in different types of cancer cells regardless of the status of macroautophagy. We also demonstrate an increase in CMA components in human cancers of different types and origins. CMA is required for cancer cell proliferation in vitro because it contributes to the maintenance of the metabolic alterations characteristic of malignant cells. Using human lung cancer xenografts in mice, we confirmed the CMA dependence of cancer cells in vivo. Inhibition of CMA delays xenograft tumor growth, reduces the number of cancer metastases, and induces regression of existing human lung cancer xenografts in mice. The fact that similar manipulations of CMA also reduce tumor growth of two different melanoma cell lines suggests that targeting this autophagic pathway may have broad antitumorigenic potential.