Frequency and longitudinal clinical outcomes of Alzheimer's AT(N) biomarker profiles: A longitudinal study.

INTRODUCTION: We aimed to estimate the frequency of each AT(N) (ß-amyloid deposition [A], pathologic tau [T], and neurodegeneration [N]) profile in different clinical diagnosis groups and to describe the longitudinal change in clinical outcomes of individuals in each group. METHODS: Longitudinal change in clinical outcomes and conversion risk of AT(N) profiles are assessed using linear mixed-effects models and multivariate Cox proportional-hazard models, respectively. RESULTS: Participants with A+T+N+ showed faster clinical progression than those with A-T-N- and A+T±N-. Compared with A-T-N-, participants with A+T+N± had an increased risk of conversion from cognitively normal (CN) to incident prodromal stage of Alzheimer's disease (AD), and from MCI to AD dementia. A+T+N+ showed an increased conversion risk when compared with A+T±N-. DISCUSSION: The 2018 research framework may provide prognostic information of clinical change and progression. It may also be useful for targeted recruitment of participants with AD into clinical trials.

Immune Checkpoint Inhibitor-Associated Systemic Sclerosis in the Treatment of a Small Cell Lung Cancer Patient with Durvalumab: A Case Report.

As one of the key cancer treatment measures, immune-checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of various cancers, including malignancies previously thought to be untreatable. Immune checkpoint inhibitors work by targeting the dysfunctional immune system, to enhance cancer-cell killing by CD8-positive T cells. Despite the beneficial effects of ICIs, these treatments are also linked to a novel class of side effects, termed immune-related adverse events (irAEs). Immune-related adverse events can affect multiple organ systems, such as endocrine, neurological, gastroenteric, dermatologic, ocular, hepatic, renal, and rheumatic ones. While variable in severity, irAEs can be associated with significant morbidity, mortality, cessation of ICI treatment and can be potentially life-threatening sometimes. Among varieties of irAEs, dermatological manifestations are frequently reported, since they can be easily observed. Here, we present a case of a 74-year-old patient with widespread fibrosis of skin, eventually diagnosed as diffuse cutaneous systemic sclerosis after the treatment with durvalumab for small cell lung cancer (SCLC). Prompt recognition and treatment of immune-checkpoint inhibitors-associated systemic sclerosis may help enhance tolerance to ICIs and ensure better performance in treating tumors.