This review details tumor necrosis factor alpha (TNF) biology and its role in sleep, and describes how TNF medications influence sleep/wake activity. Substantial evidence from healthy young animals indicates acute enhancement or inhibition of endogenous brain TNF respectively promotes and inhibits sleep. In contrast, the role of TNF in sleep in most human studies involves pathological conditions associated with chronic elevations of systemic TNF and disrupted sleep. Normalization of TNF levels in such patients improves sleep. A few studies involving normal healthy humans and their TNF levels and sleep are consistent with the animal studies but are necessarily more limited in scope. TNF can act on established sleep regulatory circuits to promote sleep and on the cortex within small networks, such as cortical columns, to induce sleep-like states. TNF affects multiple synaptic functions, e.g., its role in synaptic scaling is firmly established. The TNF-plasticity actions, like its role in sleep, can be local network events suggesting that sleep and plasticity share biochemical regulatory mechanisms and thus may be inseparable from each other. We conclude that TNF is involved in sleep regulation acting within an extensive tightly orchestrated biochemical network to niche-adapt sleep in health and disease.
Highlights The endothelial glycocalyx is a ubiquitous intravascular structure essential for vascular homeostasis. During sepsis, the glycocalyx is degraded via the collective action of a variety of redundant sheddases, the regulation of which remains the focus of active investigation. Septic loss of the glycocalyx imparts both local vascular injury (leading to acute respiratory distress syndrome and acute kidney injury) as well as the systemic consequences of circulating glycosaminoglycan fragments (leading to cognitive dysfunction). Glycocalyx degradation during sepsis is potentially shaped by clinically-modifiable factors, suggesting opportunities for therapeutic intervention to mitigate the end-organ consequences of sepsis.
Older patients represent an inordinate proportion of intensive care unit (ICU) admissions and ICU mortality associated with coronavirus disease 2019 (COVID-19). In this retrospective cohort study, we examine 198 patients, aged 18 years or older, admitted to the ICU from March to June 2020. We aim to understand the relationships between age, number of comorbidities, and independent living prior to admission on outcomes of mortality, length of stay, renal failure, respiratory failure, and shock. In this cohort, we find that overall mortality was associated with respiratory failure severity (for every decrease of P:F by 50, odds ratio (OR) 2.98 (1.65–6.08)), acute renal failure (OR 4.61 (1.2–19.7)), and age 65 or greater (OR: 3.7 (1.86–7.36)). Surprisingly, increasing age was associated with less severe respiratory failure (R = 0.22, p < 0.01). When adjusting for pre-existing chronic kidney disease, age was not associated with development of acute kidney injury (OR: 1.01 (0.99–1.03)). While chronologic age is associated with mortality, it is not associated independently with severe end organ damage. This is consistent with growing evidence suggesting that a complex interplay between multimorbidity, immunosenescence, and physiologic age is primarily responsible for the vulnerability to COVID-19.
Legal status in the United States is an important social determinant of health. Undocumented immigrants face several obstacles in obtaining equivalent healthcare to United States citizens or resident aliens. Despite these obstacles, undocumented individuals are eligible to be listed for and receive organ transplant for advanced disease. We hypothesize that this population represents healthy workers, and has significantly different social and clinical needs pre-transplantation than the population of listed US Citizens or resident aliens. We sought to describe this population of undocumented patients, listed for lung transplantation, for the first time, to identify potential disparities in care and develop strategies to address the needs of this unique patient population.METHODS: Using the de-identified United Network for Organ Sharing (UNOS) Thoracic dataset we identified 64,585 individuals who had been listed for lung transplant between 1985 and 2020. We identified 232 undocumented individuals; nonresident aliens who did not travel to the US for the purpose of transplant evaluation or have their care paid for by a foreign healthcare system. We evaluated demographic, disease characteristic, and payer differences between documented and undocumented individuals using bivariate tests of difference. We report Cohen's d statistics, when possible, to characterize the degree of difference between the two populations. RESULTS:The mean age of undocumented individuals listed for transplant was 41.1 years, which was significantly lower than that of documented individuals (p < 0.00001). The proportion of individuals with the listing diagnoses of idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), and bronchiectasis was significantly higher in the undocumented cohort of patients (p-values of 0.002, < 0.001, and <0.001 respectively). However, the proportion of undocumented individuals with a listing diagnosis of chronic obstructive pulmonary disease (COPD) was significantly lower (p < 0.001). Patients within the undocumented cohort also had a higher initial Lung Allocation Score (LAS) than documented individuals with an average score of 43.1 indicating more severe disease (p = 0.046). Undocumented individuals were less likely to have a history of tobacco use (p < 0.001). The majority of undocumented individuals were self-pay and there were no significant differences in Medicaid users between both cohorts. CONCLUSIONS: Undocumented patients listed for lung transplant represent a younger population of non-smokers who likely have very different medical and social needs than US citizens or resident aliens. Further evaluation of the specific needs of this population is warranted, particularly in areas with high populations of undocumented individuals.CLINICAL IMPLICATIONS: These patients are not more likely than US citizens or resident aliens to rely on public insurance programs (e.g. Medicare and Medicaid) indicating that the current practice of listing these individuals does not place an excessive burden on...
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