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Frequently asked questions on surrogate endpoints in oncology-opportunities, pitfalls, and the way forward.
EClinicalMedicine
October 2024
Department of Oncology, Queen's University, Kingston, Canada.
Patients with cancer expect prolonged life (overall survival, OS) or better life (quality of life, QOL) from cancer treatments. However, majority of new cancer drugs are now being approved not based on improved OS or QOL, but based on surrogate endpoints such as tumor shrinkage or delayed tumor progression. These surrogate endpoints, including their validity as a proxy for overall survival, differ based on disease settings and lines of treatment but in general, most surrogate measures have weak correlation with outcomes that matter to patients.
View Article and Find Full Text PDFIsolation and characterization of cellulose-mineralizing haloalkaliphilic bacteria from Siberian soda lakes.
Front Microbiol
December 2024
Winogradsky Institute of Microbiology, Federal Research Centre of Biotechnology, Russian Academy of Sciences, Moscow, Russia.
Soda lakes are unique double-extreme habitats characterized by high salinity and soluble carbonate alkalinity, yet harboring rich prokaryotic life. Despite intensive microbiology studies, little is known about the identity of the soda lake hydrolytic bacteria responsible for the primary degradation of the biomass organic matter, in particular cellulose. In this study, aerobic and anaerobic enrichment cultures with three forms of native insoluble cellulose inoculated with sediments from five soda lakes in south-western Siberia resulted in the isolation of four cellulotrophic haloalkaliphilic bacteria and their four saccharolytic satellites.
View Article and Find Full Text PDFWe hypothesized that outborn neonates from smaller birth volume hospitals would have more frequent adverse short-term outcomes following therapeutic hypothermia (TH). Multicenter retrospective study comparing outcomes for small (<500 births/year), medium (501-1500 births/year), and large (>1500 births/year) hospitals in Northern New England. Multivariable logistic regression assessed the combined outcome of death/severe gray matter injury on MRI, controlling for encephalopathy severity and time to initiation of TH.
View Article and Find Full Text PDFBackground: Perivascular Spaces (PVS) are a marker of cerebral small vessel disease (CSVD) that are visible on brain imaging. Larger PVS has been associated with poor quality of life and cognitive impairment post-stroke. However, the association between PVS and post-stroke sensorimotor outcomes has not been investigated.
View Article and Find Full Text PDFCerebral perfusion alterations in healthy young adults due to two genetic risk factors of Alzheimer's disease: APOE and MAPT.
J Cereb Blood Flow Metab
January 2025
Sheffield Institute for Translational Neuroscience, Division of Neuroscience, School of Medicine and Population Heath, University of Sheffield, Sheffield, UK.
Functional brain changes such as altered cerebral blood flow occur long before the onset of clinical symptoms in Alzheimer's disease (AD) and other neurodegenerative disorders. While cerebral hypoperfusion occurs in established AD, middle-aged carriers of genetic risk factors for AD, including APOE ε4, display regional hyperperfusion due to hypothesised pleiotropic or compensatory effects, representing a possible early biomarker of AD and facilitating earlier AD diagnosis. However, it is not clear whether hyperperfusion already exists even earlier in life.
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