Journal of internal medicine
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Recent genomic studies revealed enhancer of zeste homolog 2 (EZH2) gain-of-function mutations, representing novel therapeutic targets in follicular lymphoma (FL) in around one quarter of patients. However, these analyses relied on single-site tissue biopsies and did not investigate the spatial heterogeneity and temporal dynamics of these alterations. ⋯ The in-depth spatio-temporal analysis identified EZH2 mutations in a considerably higher proportion of patients than previously reported. This expands the subset of FL patients who most likely would benefit from EZH2 inhibitor therapy.
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Acute SARS-COVID-19 infection may increase readmission risk compared to other respiratory infections. We assessed the 1-year readmission and inhospital death rates of hospitalized SARS-COVID-19 patients compared to patients hospitalized with other types of pneumonia. ⋯ The 1-year readmission rate in COVID-19 patients was 6.6% (328/50,067) versus 8.5% in pneumonia patients (4699/55,439; p < 0.001), with an inhospital mortality rate of 7.7% (n = 251) and 9.7% (n = 454; p = 0.002) for COVID-19 and pneumonia patients, respectively.
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The prevalence of cognitive dysfunction, dementia, and neurodegenerative disorders such as Alzheimer's disease (AD) is increasing in parallel with an aging population. Distinct types of chronic stress are thought to be instrumental in the development of cognitive impairment in central nervous system (CNS) disorders where cognitive impairment is a major unmet medical need. Increased GABAergic tone is a mediator of stress effects but is also a result of other factors in CNS disorders. ⋯ In transgenic AD animal studies, continuous exposure to ALLO at physiological levels impairs cognition and increases degenerative AD pathology, whereas intermittent ALLO injections enhance cognition, indicating pleiotropic functions of ALLO. We have shown that GABA-A receptor modulating steroid antagonists (GAMSAs) can block the acute negative cognitive impairment of ALLO on memory in animal studies and in patients with cognitive impairment due to hepatic encephalopathy. Here we describe disorders affected by steroid-PAMs and opportunities to treat these adverse effects of steroid-PAMs with novel GAMSAs.
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Craniopharyngiomas (CPs) are rare primary brain epithelial tumors arising in the suprasellar region from remnants of Rathke's pouch. About 50% originate at the level of the third ventricle floor, including the hypothalamus (HT). CPs are characterized by a low proliferation rate and symptoms due to mass effect and local infiltration and are managed primarily with surgery and radiotherapy. ⋯ The group with HT damage suffers from cognitive dysfunction with attention deficits, impaired episodic memory, and processing speed. Diffusion tensor imaging has shown significant microstructural white matter alteration in several areas important for cognition. Recently, complete or partial tumor response was shown to targeted therapy, with BRAF and Mekinist inhibitors for PCPs with BRAF V600E mutation.
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Neurotensin (NT), an intestinal peptide able to promote fat absorption, is implicated in the pathogenesis of obesity. Increased levels of proneurotensin (pro-NT), a stable NT precursor fragment, have been found in subjects with nonalcoholic fatty liver disease (NAFLD); however, whether higher pro-NT levels are associated with an increased NAFLD risk independently of other metabolic risk factors is unsettled. ⋯ Higher pro-NT levels are a predictor of NAFLD independent of other metabolic risk factors.