Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.

Wiskott-Aldrich syndrome (WAS) is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.

Optimising cell-based bioassays via integrated design of experiments (ixDoE) - A practical guide.

For process optimisation Design of Experiments (DoE) has long been established as a more powerful strategy than a One Factor at a Time approach. Nevertheless, DoE is not widely used especially in the field of cell-based bioassay development although it is known that complex interactions often exist. We believe that biopharmaceutical manufacturers are reluctant to move beyond standard practices due to the perceived costs, efforts, and complexity.

The AICD fragment of APP initiates a FoxO3a mediated response via FANCD2.

The amyloid precursor protein (APP) is a cell surface protein of uncertain function that is notable for being the parent protein of beta-amyloid. Research around this protein has focussed heavily on the link to Alzheimer's disease and neurodegeneration. However, there is increasing evidence that APP may be linked to neuronal loss through mechanisms independent of beta-amyloid.

Estimands for overall survival in clinical trials with treatment switching in oncology.

An addendum of the ICH E9 guideline on Statistical Principles for Clinical Trials was released in November 2019 introducing the estimand framework. This new framework aims to align trial objectives and statistical analyses by requiring a precise definition of the inferential quantity of interest, that is, the estimand. This definition explicitly accounts for intercurrent events, such as switching to new anticancer therapies for the analysis of overall survival (OS), the gold standard in oncology.

Real-world efficacy of docetaxel plus nintedanib after chemo-immunotherapy failure in advanced pulmonary adenocarcinoma.

This real-world analysis evaluated docetaxel plus nintedanib in patients with advanced pulmonary adenocarcinoma after chemotherapy and immune checkpoint inhibitor failure, for whom treatment options are limited. Data were sourced retrospectively from seven German centers. Of 93 patients, overall response rate was 41.