The effect of phototherapy on progression to tumors in patients with patch and plaque stage of mycosis fungoides.

BACKGROUND: Phototherapy has been a mainstay in the treatment of mycosis fungoides (MF). However, the recent findings of UV-induced p53 mutations in advanced MF suggest that phototherapy may contribute to disease progression. OBJECTIVE: The objective of this study was to evaluate the effect of phototherapy on the time to tumor progression and overall survival in MF. MATERIALS AND METHODS: Retrospective analysis of patients seen at the University of Pittsburgh Cutaneous Lymphoma Clinic from 1979 to 2016. RESULTS: A total of 345 patients with MF were identified. 258 (74.8%) were diagnosed at stage IA or IB. 43 out of the 258 (16.6%) progressed to tumor stage. Before tumor development, 30 out of the 43 (69.8%) patients received phototherapy, and 13 (30.2%) did not. Patients who received phototherapy had a longer median time to tumor progression than those who did not: 3.5 years (interquartile range = 1.9-5.7) versus 1.2 years (0.2-2.3) (p = .001). Patients who received phototherapy also survived longer: 6.9 years (interquartile range = 4.3-9.5) versus 3.8 years (3.0-4.5) (p = .014). LIMITATIONS: Limited information on specific phototherapy start dates, durations, and treatment protocols. CONCLUSIONS: The therapeutic effects of phototherapy, with longer times to tumor progression and increased overall survival, appear to outweigh its potential adverse effects.

Subjective-Objective Sleep Discrepancy in Older Adults With MCI and Subsyndromal Depression.

BACKGROUND/OBJECTIVES: We investigated the prevalence and correlates of discrepancies between self-reported sleep quality (Pittsburgh Sleep Quality Index) and objective sleep efficiency (actigraphy) in older adults with mild cognitive impairment (MCI) and subsyndromal depression. METHODS: This was a secondary analysis of a clincial trial with 59 adults aged 60 years and older with MCI and subsyndromal depression. We included baseline data on participants' subjective sleep quality, objective sleep efficiency, depressive symptoms, insomnia diagnosis, and cognitive functioning. RESULTS: Pittsburgh Sleep Quality Index subjective sleep quality and actigraphy-measured sleep efficiency were not significantly correlated ( r = -.06; P = .64), with 61% of participants having subjective-objective sleep discrepancies. Correlates of subjective-objective sleep discrepancy included the presence of an insomnia diagnosis and impaired memory, particularly delayed memory. CONCLUSION: These findings are important because subjective underestimation of symptoms in older adults with memory impairments may result in sleep disturbances going unrecognized in clinical practice; on the other hand, an insomnia disorder may be a possible remediable contribution to subjective overestimation of sleep disturbances.

Prolonged triglyceride storage in macrophages: pHo trumps pO2 and TLR4.

Lipid-laden macrophages contribute to pathologies as diverse as atherosclerosis and tuberculosis. Three common stimuli are known to promote macrophage lipid storage: low tissue oxygen tension (pO2), low extracellular pH (pHo), and exposure to agonists such as bacterial LPS. Noting that cells responding to low pO2 or agonistic bacterial molecules often decrease pHo by secreting lactic and other carboxylic acids, we studied how pHo influences the stimulation of triacylglycerol (TAG) storage by low pO2 and LPS. We found that TAG retention after incubation for 48-72 h was inversely related to pHo when primary macrophages were cultured in 21% oxygen, 4% oxygen, or with LPS at either oxygen concentration. Maintaining pHo at ~7.4 was sufficient to prevent the increase in prolonged TAG storage induced by either low pO2 or LPS. The strong influence of pHo on TAG retention may explain why lipid-laden macrophages are found in some tissue environments and not in others. It is also possible that other long-term cellular changes currently attributed to low pO2 or bacterial agonists may be promoted, at least in part, by the decrease in pHo that these stimuli induce.

Toll-like receptor agonists promote prolonged triglyceride storage in macrophages.

Macrophages in infected tissues may sense microbial molecules that significantly alter their metabolism. In a seeming paradox, these critical host defense cells often respond by increasing glucose catabolism while simultaneously storing fatty acids (FA) as triglycerides (TAG) in lipid droplets. We used a load-chase strategy to study the mechanisms that promote long term retention of TAG in murine and human macrophages. Toll-like receptor (TLR)1/2, TLR3, and TLR4 agonists all induced the cells to retain TAG for ≥3 days. Prolonged TAG retention was accompanied by the following: (a) enhanced FA uptake and FA incorporation into TAG, with long lasting increases in acyl-CoA synthetase long 1 (ACSL1) and diacylglycerol acyltransferase-2 (DGAT2), and (b) decreases in lipolysis and FA ß-oxidation that paralleled a prolonged drop in adipose triglyceride lipase (ATGL). TLR agonist-induced TAG storage is a multifaceted process that persists long after most early pro-inflammatory responses have subsided and may contribute to the formation of "lipid-laden" macrophages in infected tissues.