Phase 1/2 trial of avelumab combined with utomilumab (4-1BB agonist), PF-04518600 (OX40 agonist), or radiotherapy in patients with advanced gynecologic malignancies.

Background: Immune checkpoint blockade has shown mixed results in advanced/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4-1BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4-1BB agonist), PF-04518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies.

Clinical outcomes at medium-term follow-up of COVID-19.

Background: The long coronavirus disease 2019 (COVID-19) syndrome is defined as persistent physical, cognitive and/or psychological symptoms that continue for more than 12 weeks following the acute illness.

Methods: In all, 2,646 patients were randomly selected from all individuals who were diagnosed with COVID-19. They were interviewed so as to assess the persistence of symptoms and health-related quality of life.

Clinical Outcomes of Patients with Recurrent Microsatellite-Stable Endometrial Cancer in Early-Phase Immunotherapy Clinical Trials.

Recurrent microsatellite stable (MSS) endometrial cancer has poor response to conventional therapy and limited efficacy with immune checkpoint monotherapy. We conducted a retrospective study of recurrent MSS endometrial cancer patients enrolled in immunotherapy-based clinical trials at MD Anderson Cancer Center between 1 January 2010 and 31 December 2019. Patients were evaluated for radiologic response using RECIST 1.

Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys.

In nonhuman primates we tested a new set of behavioral categories for observable sedative effects using pediatric anesthesiology classifications as a basis. Using quantitative behavioral observation techniques in rhesus monkeys, we examined the effects of alprazolam and diazepam (nonselective benzodiazepines), zolpidem (preferential binding to 1 subunit-containing GABA receptors), HZ-166 (8-ethynyl-6-(2'-pyridine)-4-2,5,10b-triaza-benzo[]azulene-3-carboxylic acid ethyl ester; functionally selective with relatively high intrinsic efficacy for 2 and 3 subunit-containing GABA receptors), MRK-696 [7-cyclobutyl-6-(2-methyl-2-1,2,4-triazol-2-ylmethoxy)-3-(2-flurophenyl)-1,2,4-triazolo(4,3-)pyridazine; no selectivity but partial intrinsic activity], and TPA023B 6,2'-diflouro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile; partial intrinsic efficacy and selectivity for 2, 3, 5 subunit-containing GABA receptors]. We further examined the role of 1 subunit-containing GABA receptors in benzodiazepine-induced sedative effects by pretreating animals with the 1 subunit-preferring antagonist -carboline-3-carboxylate--butyl ester (CCT).

Brain amyloid load and its associations with cognition and vascular risk factors in FINGER Study.

Objective: To investigate brain amyloid pathology in a dementia-risk population defined as cardiovascular risk factors, aging, and dementia risk (CAIDE) score of at least 6 but with normal cognition and to examine associations between brain amyloid load and cognitive performance and vascular risk factors.

Methods: A subgroup of 48 individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in brain C-Pittsburgh compound B (PiB)-PET imaging, brain MRI, and neuropsychological assessment at the beginning of the study. Lifestyle/vascular risk factors were determined as body mass index, blood pressure, total and low-density lipoprotein cholesterol, and glucose homeostasis model assessment.