Longitudinal Evaluation of Individuals With Severe Alpha-1 Antitrypsin Deficiency (Pi∗ZZ Genotype).

Background & Aims: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints.

Methods: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM).

Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression.

In advanced prostate cancer (PC), in particular after acquisition of resistance to androgen receptor (AR) signaling inhibitors (ARSI), upregulation of AR splice variants compromises endocrine therapy efficiency. Androgen receptor splice variant-7 (ARV7) is clinically the most relevant and has a distinct 3' untranslated region (3'UTR) compared to the AR full-length variant, suggesting a unique post-transcriptional regulation. Here, we set out to evaluate the applicability of the ARV7 3'UTR as a therapy target.

Sub-optimal therapy of patients with primary biliary cholangitis (PBC) in the real-life stetting of the German PBC cohort.

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.