New Potent Inhibitor of Transforming Growth Factor-Beta (TGFβ) Signaling that is Efficacious against Microsatellite Stable Colorectal Cancer Metastasis in Combination with Immune Checkpoint Therapy in Mice.

Blockade of the TGFβ signaling pathway has emerged from preclinical studies as a potential treatment to enhance the efficacy of immune checkpoint inhibition in advanced colorectal cancer (CRC) and several other types of cancer. However, clinical translation of first-generation inhibitors has shown little success. Here, we report the synthesis and characterization of HYL001, a potent inhibitor of TGFβ receptor 1 (ALK5), that is approximately 9 times more efficacious than the structurally related compound galunisertib, while maintaining a favorable safety profile.

Effect of a competence based medical education program on training quality in Intensive Care Medicine. COBALIDATION TRIAL.

Objectives: The main objective of this study was to evaluate whether the implementation of CoBaTrICE (Competency-Based Training in Intensive Care Medicine in Europe) provides higher levels of competency in comparison with the current official time-based program in Intensive Care Medicine in Spain. Secondary objectives were: 1) To determine the percentage of critical essential performance elements (CEPE) accomplished, 2) To determine compliance with workplace-based assessments (wba).

Design: Multicenter cluster randomized trial.

Danio rerio embryo as in vivo model for the evaluation of the toxicity and metabolism of pyrovalerone cathinones.

The objective of the present manuscript was the evaluation of the toxicity and metabolism of the second generation of pyrovalerone cathinones (α-PHP, α-PHPiP, 4-MePPP and TH-PVP), using an early zebrafish (Danio rerio) larvae as in vivo model. Pyrovalerone cathinones LC were determined after 24, 48, 72 and 96 h of exposure. TH-PVP proved to be the most toxic cathinone, whereas 4-MePPP was the least toxic.

Efficacy of escalating therapy with brentuximab vedotin-AVD in advanced stage Hodgkin lymphoma patients with positive interim positron emission tomography after ABVD.

Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification.