Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.

Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR).

Independent associations of sleep and physical activity with cognition are mediated by hippocampal microstructure in middle-aged and older adults.

Sleep and physical activity levels are both associated with cognitive performance among older adults; however, the brain mechanisms underlying these beneficial relationships remain poorly understood. This study investigated cross-sectional associations of actigraphic estimates of physical activity and sleep with cognition and diffusion imaging-based measures of medial temporal lobe (MTL) gray matter microstructural integrity in adults free of dementia. Participants were 132 older adults from the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) cohort study (119 cognitively unimpaired and 13 with mild cognitive impairment; mean age=70.

Sleep and Depressive Symptoms in Sedentary Community-Dwelling Older Adults With Sleep Complaints: Findings From Ambulatory Sleep EEG.

Background: There is limited and inconsistent evidence on the association between electroencephalography (EEG) measured sleep and depressive symptoms among community-dwelling older adults. This study aimed to investigate the cross-sectional association between EEG-measured sleep and depressive symptoms.

Methods: Using baseline data from a randomized clinical trial, we included 66 sedentary community-dwelling older adults with sleep complaints (≥ 1 self-reported insomnia symptom).

Novel applications of sleep pharmacology as delirium therapeutics.

Sleep-wake and circadian disruption (SCD) is a core feature of delirium. It has been hypothesized that SCD contributes to delirium pathogenesis; therefore, interventions that prevent or reverse SCD represent an array of promising opportunities in relation to delirium. This review explores the relationship between sleep-wake/circadian physiology and delirium pathophysiology with a focus on neurotransmitter systems.

A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST).

 Alzheimer's disease (AD) is a leading cause of mortality and morbidity among aging populations worldwide. Despite arduous research efforts, treatment options for this devastating neurodegenerative disease are limited. Sleep disturbances, through their link to changes in neural excitability and impaired clearance of interstitial abnormal protein aggregates, are a key risk factor for the development of AD.

Latent classes of sleep problems and subjective cognitive decline among middle-aged and older adults in the United States.

Objective: Previous studies have linked sleep problems to subjective cognitive decline (SCD) using a variable-centered approach (e.g., adding sleep symptoms to form a score); however, sleep problems may cluster differently between individuals.

Real-world comparative effectiveness of sotorasib versus docetaxel in second line and beyond among patients with advanced non-small cell lung cancer (NSCLC).

Objectives: To evaluate the comparative effectiveness of sotorasib monotherapy versus docetaxel as monotherapy or combination therapy in patients with pretreated KRAS G12C-mutated advanced NSCLC in the real-world.

Methods: A US-based electronic health record-derived de-identified database was used in this study. Patients with pretreated KRAS G12C-mutated advanced NSCLC who initiated sotorasib between May 28, 2021, and September 30, 2022, and docetaxel between January 1, 2019, and September 30, 2022 (to enhance sample size), were included, with a minimum of 12-month opportunity for follow-up.

Association of inadequate sleep with mortality among persons who inject drugs.

Background: Inadequate sleep is associated with all-cause mortality in the general population. Substance use has adverse effects on sleep, and insomnia symptoms are common among people with HIV. Therefore, persons who inject drugs may face a heightened risk of adverse outcomes from inadequate sleep.

ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors.

Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.

Patients And Methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.

Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer.

Purpose: Patients with advanced endometrial cancer (EC) who progress on or after platinum-based therapy and immunotherapy have poor prognosis. We report efficacy and safety of sacituzumab govitecan (SG), a trophoblast cell-surface antigen 2 (Trop-2)-directed antibody-drug conjugate, in patients with advanced EC.

Methods: TROPiCS-03 (ClinicalTrials.

Sleep-related impairment among people who use opioids: The critical role of structural vulnerability.

Objective: People who use opioids are vulnerable to sleep disturbances due to a range of factors, including the substances they use and the various structural vulnerabilities they face. We aimed to understand the burden of sleep-related impairment and problems pertaining to sleep context and schedule among people who use opioids.

Methods: We explored sleep quality and problems among a suburban sample of people who use opioids experiencing extensive structural vulnerabilities (N = 170).

Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma.

Purpose: Coblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma.

The evolution of lung adenocarcinoma precursors is associated with chromosomal instability and transition from innate to adaptive immune response/evasion.

Studying lung adenocarcinoma (LUAD) early carcinogenesis is challenging, primarily due to the lack of LUAD precursors specimens. We amassed multi-omics data from 213 LUAD and LUAD precursors to identify molecular features underlying LUAD precancer evolution. We observed progressively increasing mutations, chromosomal aberrations, whole genome doubling and genomic instability from precancer to invasive LUAD, indicating aggravating chromosomal instability (CIN).

Sleep Quality Moderates the Associations between Cardiorespiratory Fitness and Hippocampal and Entorhinal Volume in Middle-Aged and Older Adults.

Introduction/purpose: As individuals age, the entorhinal cortex (ERC) and hippocampus-crucial structures for memory-tend to atrophy, with related cognitive decline. Simultaneously, lifestyle factors that can be modified, such as exercise and sleep, have been separately linked to slowing of brain atrophy and functional decline. However, the synergistic impact of fitness and sleep on susceptible brain structures in aging adults remains uncertain.

Differences in Daily Physical Activity by Alzheimer's Risk Markers Among Older Adults.

Background: Daily physical activity patterns differ by Alzheimer's disease (AD) status and might signal cognitive risk. It is critical to understand whether patterns are disrupted early in the AD pathological process. Yet, whether established AD risk markers (β-amyloid [Aβ] or apolipoprotein E-ε4 [APOE-ε4]) are associated with differences in objectively measured activity patterns among cognitively unimpaired older adults is unclear.