Acute saddle pulmonary embolism on 18F-FDG PET/CT: diagnosis by functional imaging.

18F-labelled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is used extensively in the setting of cancer staging and in assessing cancer treatment response. Oncology patients have a sevenfold risk of developing pulmonary embolism (PE) due to underlying activation of the haemostatic system and anti-cancer therapy inducing a hypercoagulable state. The diagnosis of PE on 18F-FDG PET/CT is challenging, particularly in the absence of intravenous contrast. The case of a female patient undergoing treatment for advanced diffuse large B-cell lymphoma is presented. The ancillary signs of PE are illustrated on consecutive non-contrast-enhanced 18F-FDG PET/CT scans. The signs include the "rim sign" relating to regions of pulmonary infarction and abnormal cardiac uptake indicating right heart strain. The diagnosis was confirmed on CT pulmonary angiography which demonstrated extensive PE, including a saddle embolus.

Advanced nanotechnology: An arsenal to enhance immunotherapy in fighting cancer.

Cancer remains a major disease process with considerable healthcare and socioeconomic impact worldwide. Unfortunately, standard treatments using chemotherapy often do not effectively control cancer progression or prevent relapse. Over the past decades, the development of targeted therapies has substantially improved outcomes. Recently, immunotherapy has emerged as a new alternative for more effective cancer treatment and may even bring hope of a cure. Cancer immunotherapy functions by reinforcing a patient's immune defense system to fight the disease. Clinically, promising immunotherapy approaches have, however, been limited by unpredictable response and strong adverse effects. A drug delivery system (DDS) that effectively targets tumor and reduces drug exposure to normal tissue would mitigate these limitations. In this regard, nanotechnology has been intensively studied as a DDS for targeting tumors with various oncologic drugs. Several have resulted in improved treatment and outcome. Research has shown that nanoparticle drug delivery technologies can also be applied to immunotherapy. In this review, the current state of nanotechnology will be discussed. Because most cancer immunotherapies approved in recent years are protein drugs, this article will focus on a micellar nanocomplex (MNC) technology, a DDS platform especially suited for targeted delivery of these therapeutics to solid tumors.

Individual differences in physiologic measures are stable across repeated exposures to total sleep deprivation.

Some individuals show severe cognitive impairment when sleep deprived, whereas others are able to maintain a high level of performance. Such differences are stable and trait-like, but it is not clear whether these findings generalize to physiologic responses to sleep loss. Here, we analyzed individual differences in behavioral and physiologic measures in healthy ethnic-Chinese male volunteers (n = 12; aged 22-30 years) who were kept awake for at least 26 h in a controlled laboratory environment on two separate occasions. Every 2 h, sustained attention performance was assessed using a 10-min psychomotor vigilance task (PVT), and sleepiness was estimated objectively by determining percentage eyelid closure over the pupil over time (PERCLOS) and blink rate. Between-subject differences in heart rate and its variability, and electroencephalogram (EEG) spectral power were also analyzed during each PVT. To assess stability of individual differences, intraclass correlation coefficients (ICC) were determined using variance components analysis. Consistent with previous work, individual differences in PVT performance were reproducible across study visits, as were baseline sleep measures prior to sleep deprivation. In addition, stable individual differences were observed during sleep deprivation for PERCLOS, blink rate, heart rate and its variability, and EEG spectral power in the alpha frequency band, even after adjusting for baseline differences in these measures (range, ICC = 0.67-0.91). These findings establish that changes in ocular, ECG, and EEG signals are highly reproducible across a night of sleep deprivation, hence raising the possibility that, similar to behavioral measures, physiologic responses to sleep loss are trait-like.

Effects of exposure to intermittent versus continuous red light on human circadian rhythms, melatonin suppression, and pupillary constriction.

Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21-28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm(-2) s(-1)), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light.

Sustained attention performance during sleep deprivation associates with instability in behavior and physiologic measures at baseline.

STUDY OBJECTIVES: To identify baseline behavioral and physiologic markers that associate with individual differences in sustained attention during sleep deprivation. DESIGN: In a retrospective study, ocular, electrocardiogram, and electroencephalogram (EEG) measures were compared in subjects who were characterized as resilient (n = 15) or vulnerable (n = 15) to the effects of total sleep deprivation on sustained attention. SETTING: Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School Singapore. PARTICIPANTS: Healthy volunteers aged 22-32 years from the general population. INTERVENTIONS: Subjects were kept awake for at least 26 hours under constant environmental conditions. Every 2 hours, sustained attention was assessed using a 10-minute psychomotor vigilance task (PVT). MEASUREMENTS AND RESULTS: During baseline sleep and recovery sleep, EEG slow wave activity was similar in resilient versus vulnerable subjects, suggesting that individual differences in vulnerability to sleep loss were not related to differences in homeostatic sleep regulation. Rather, irrespective of time elapsed since wake, subjects who were vulnerable to sleep deprivation exhibited slower and more variable PVT response times, lower and more variable heart rate, and higher and more variable EEG spectral power in the theta frequency band (6.0-7.5 Hz). CONCLUSIONS: Performance decrements in sustained attention during sleep deprivation associate with instability in behavioral and physiologic measures at baseline. Small individual differences in sustained attention that are present at baseline are amplified during prolonged wakefulness, thus contributing to large between-subjects differences in performance and sleepiness.

Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans.

The circadian system regulates daily rhythms in lipid metabolism and adipose tissue function. Although disruption of circadian clock function is associated with negative cardiometabolic end points, very little is known about interindividual variation in circadian-regulated metabolic pathways. Here, we used targeted lipidomics-based approaches to profile the time course of 263 lipids in blood plasma in 20 healthy individuals. Over a span of 28 h, blood was collected every 4 h and plasma lipids were analyzed by HPLC/MS. Across subjects, about 13% of lipid metabolites showed circadian variation. Rhythmicity spanned all metabolite classes examined, suggesting widespread circadian control of lipid-mediated energy storage, transport, and signaling. Intersubject agreement for lipids identified as rhythmic was only about 20%, however, and the timing of lipid rhythms ranged up to 12 h apart between individuals. Healthy subjects therefore showed substantial variation in the timing and strength of rhythms across different lipid species. Strong interindividual differences were also observed for rhythms of blood glucose and insulin, but not cortisol. Using consensus clustering with iterative feature selection, subjects clustered into different groups based on strength of rhythmicity for a subset of triglycerides and phosphatidylcholines, suggesting that there are different circadian metabolic phenotypes in the general population. These results have potential implications for lipid metabolism disorders linked to circadian clock disruption.

Heart rate variability can be used to estimate sleepiness-related decrements in psychomotor vigilance during total sleep deprivation.

STUDY OBJECTIVES: To assess whether changes in psychomotor vigilance during sleep deprivation can be estimated using heart rate variability (HRV). DESIGN: HRV, ocular, and electroencephalogram (EEG) measures were compared for their ability to predict lapses on the Psychomotor Vigilance Task (PVT). SETTING: Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School Singapore. PARTICIPANTS: Twenty-four healthy Chinese men (mean age ± SD = 25.9 ± 2.8 years). INTERVENTIONS: Subjects were kept awake continuously for 40 hours under constant environmental conditions. Every 2 hours, subjects completed a 10-minute PVT to assess their ability to sustain visual attention. MEASUREMENTS AND RESULTS: During each PVT, we examined the electrocardiogram (ECG), EEG, and percentage of time that the eyes were closed (PERCLOS). Similar to EEG power density and PERCLOS measures, the time course of ECG RR-interval power density in the 0.02-0.08-Hz range correlated with the 40-hour profile of PVT lapses. Based on receiver operating characteristic curves, RR-interval power density performed as well as EEG power density at identifying a sleepiness-related increase in PVT lapses above threshold. RR-interval power density (0.02-0.08 Hz) also classified subject performance with sensitivity and specificity similar to that of PERCLOS. CONCLUSIONS: The ECG carries information about a person's vigilance state. Hence, HRV measures could potentially be used to predict when an individual is at increased risk of attentional failure. Our results suggest that HRV monitoring, either alone or in combination with other physiologic measures, could be incorporated into safety devices to warn drowsy operators when their performance is impaired.