Abstract
Introduction
Slow waves and spindles are essential oscillations occurring during NREM sleep that may be disrupted by moderate to severe traumatic brain injury (TBI). We investigated these ...oscillations in the acute and chronic trauma stage.
Methods
Four groups were tested with whole-night polysomnography: hospitalized patients with acute TBI (n=10, 29.7±13.8y) or severe orthopedic injuries (n=15, 39.9±17.1y), chronic TBI including 9 returning from the acute TBI group (n=43, 31.9±13.5y), and healthy controls (n=36, 30.5±12.7y). Characteristics for slow waves (density, amplitude, slope, frequency, duration) and spindles (density, amplitude, frequency, duration) were quantified over N2 and N3 sleep for the first three sleep cycles, and groups were compared using one-way ANOVAs.
Results
One-way ANOVAs showed group effects only for slow wave density (F=4.11 to 6.04, p=0.009 to 0.0008)) and spindle density (F=3.3 to 8.8, p=0.02 to 0.00003). These effects were present for the 2nd and 3rd sleep cycles, but not the 1st. More specifically, slow wave density in acute TBI was higher than in controls, and returned to normal levels in the chronic stage. Conversely, spindle density in acute TBI was lower than in controls and returned to normal levels in the chronic stage. No group difference was observed for the orthopedic group.
Conclusion
Our results suggest that immediately after a severely disruptive event such as a TBI, the brain needs additional deeper sleep to recover, resulting in more slow waves but also in less spindles. These changes are only present in the 2nd and 3rd sleep cycles, reflecting an absence of the expected dissipation of slow waves, which may suggest increased homeostatic sleep pressure due to the brain injury. Limits to interpretation include the hospital environment and medication, but the absence of changes in the orthopedic group under similar conditions emphasizes the effect of the brain injury itself.
Support
Canadian Institutes of Health Research (CIHR) and Fonds de Recherche Québec-Santé (FRQS)
Individuals complaining of a delayed sleep schedule are expected to have shorter sleep duration and lower sleep quality when they must comply with morning obligations. The changes in the sleep ...schedule imposed by morning obligations may in turn decrease the stability and amplitude of their rest-activity cycle. These expectations were only partially supported in previous studies, possibly due to poor differentiation between days with mandatory or free wake times.
Fourteen college/university students (8 women) with a complaint of a late sleep schedule and a bedtime after midnight were compared to fourteen controls with an earlier sleep schedule and no complaint.
During a week of 24-h activity recording, participants specified in their sleep diary whether their wake time was free or determined by an obligation.
The number of nights with mandatory wake times was similar in the two groups. Groups were also similar for sleep duration and sleep quality over the 7 days of recording. Actigraphic sleep efficiency was the same in the two groups for both free and mandatory wake times, but subjective sleep quality decreased on the nights with mandatory wake time in both groups. On the nights with mandatory wake time, delayed participants had shorter sleep episodes and less total sleep time than controls. Rest-activity cycle amplitude was lower in the delayed group whether wake time was free or mandatory.
Sleep duration and total sleep time differed between the two groups only when wake time was mandatory. Prior to mandatory wake times, delayed participants kept the same bedtime and shortened their sleep; sleep latency and sleep efficiency were preserved but subjective sleep quality and alertness on awakening decreased compared to nights with free wake time. Lower amplitude of the rest-activity cycle in delayed subjects may reflect lifestyle differences compared to control participants.
Abstract
Introduction:
We recently demonstrated that the sleep-wake cycle is severely altered in the acute stage of moderate to severe traumatic brain injuries (TBI). In general, these patients have ...short sleep and wake bouts dispersed over the 24 h. This study aimed to explore whether early markers of TBI severity predict acute sleep-wake cycle disturbances. Moreover, it aimed to verify the relationship between the sleep-wake cycle and the acute cognitive recovery.
Methods:
We included 37 non-sedated patients (age 30 ± 14 yo, 25 males) hospitalized for moderate to severe TBI. We used two severity markers that are available in the first hours following TBI, namely the initial Glasgow Coma Scale (GCS) score and the delay to recover the ability to sustain visual fixation. Once patients had reached medical stability, we used continuous actigraphy to document the sleep-wake cycle, and a consolidated sleep-wake cycle was defined by a daytime activity ratio > 80%. A short neuropsychological assessment was performed in a subsample of 13 patients. Correlation analyses were conducted between sleep-wake variables, TBI severity markers and performance on neuropsychological tests.
Results:
Patients had a median GCS score of 7 (range 3–13) and spent 6 ± 6 days without visual fixation in the intensive care unit. Once patient had reached medical stability, they had 5 ± 4 days of non-consolidated sleep-wake cycle. The number of days without sleep-wake cycle consolidation correlated with the initial GCS score (ρ=0.35; p=0.04) and the delay before recovering visual fixation (r=0.45; p<0.01). Moreover, more altered sleep-wake cycle was associated with poorer performance on cognitive screening, episodic memory, language and logical reasoning tests carried before hospital discharge (r varying from -0.5 to -0.7, p<0.05, n=13).
Conclusion:
Our results support emerging evidence showing that early markers of TBI severity gathered in the first few hours after TBI can predict acute sleep-wake cycle alterations. The reappearance of consolidated sleep-wake cycle was associated with better cognitive recovery; still the directionality (or bidirectionality) of this relationship needs to be further investigated.
Support (If Any):
The research was supported by the Canadian Institutes of Health Research (CIHR) and by the Fonds pour la recherche du Québec, Santé (FRQS)
Deltas worldwide are at risk of elevation loss and drowning due to relative sea-level rise. Management strategies to restore or enhance sedimentation on delta plains, Sedimentation-Enhancing ...Strategies (hereafter SES), are now being pursued in many deltas but there has been limited cross-disciplinary and cross-delta review. Here we compare 21 existing and planned SES, synthesizing their physical characteristics, funding, governance arrangements, stakeholder engagement, process of implementation, environmental impact, land use change, and potential for upscaling. Strategies exist at various scales, from ~0.05 km2 - 500 km2. 79% of strategies are capable of outpacing high rates of sea-level rise. Cheaper strategies are limited to short term impacts and small spatial scales, while more expensive strategies can have longer lifetimes. Most strategies create wetlands and flood water storage. Some create opportunities for agriculture, aquaculture, housing, or recreational land use. Combinations of SES will likely be the most effective and sustainable method for maintaining elevation in river deltas.
•River deltas require sediment to maintain their elevation•Several management strategies exist in river deltas to enhance sedimentation•Strategies vary in lifetime and size (from 10–100 years & ~0.05 km2 - 500 km2)•Nearly all strategies outpace projected future rates of sea-level rise•Combinations of strategies can effectively and sustainably maintain some delta area•Prompt implementation is desired to increase chances of long-term delta sustainability
Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field ...continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro- and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold. Here, we present prevailing concepts and state of the science in NET-related research and elaborate on open questions and areas of dispute.
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•Ursodeoxycholic acid is associated with prolonged survival in primary biliary cholangitis.•This positive association is significant irrespective of age, sex, or disease stage.•The ...association remains significant in cases where the established criteria for therapeutic response are not met.
The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs liver transplant (LT)-free survival in patients with PBC.
This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability treatment weighting (IPTW).
In the 3,902 patients included, the mean (SD) age was 54.3 (11.9) years, 3,552 patients (94.0%) were female, 3,529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (interquartile range) follow-up was 7.8 (4.1–12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95% CI 78.1–81.2) among UDCA-treated patients and 60.7% (95% CI 58.2–63.4) among untreated patients (p <0.001). UDCA was associated with a statistically significant reduced risk of LT or death (hazard ratio 0.46, 95% CI 0.40–0.52; p <0.001). The hazard ratio remained statistically significant in all stages of disease. Patients classified as inadequate biochemical responders after 1 year of UDCA had a lower risk of LT or death than patients who were not treated (adjusted hazard ratio 0.56; 95% CI 0.45–0.69; p <0.001).
The use of UDCA improves LT-free survival among patients with PBC, regardless of the disease stage and the observed biochemical response. These findings support UDCA as the current universal standard of care in PBC.
In this international multicenter study of 3,902 patients with primary biliary cholangitis, we found that treatment with ursodeoxycholic acid is associated with prolonged liver transplant-free survival. This association was significant, irrespective of sex, age, or disease stage. The survival benefit remained statistically significant in patients with an incomplete biochemical response to ursodeoxycholic acid therapy.
Abstract
Study Objectives
To test whether the sleep-wake cycle disruption in patients hospitalized with traumatic brain injury (TBI) (1) is also found in patients with traumatic injuries other than ...TBI (non-TBI) and (2) is associated with a weaker or abnormal circadian clock signal.
Methods
Forty-two non-mechanically ventilated and non-sedated patients hospitalized for moderate-to-severe TBI were compared to 34 non-TBI patients. They wore wrist actigraphs for 9.4 ± 4.2 days, starting 19.3 ± 12.6 days post-injury. Of these, 17 TBI and 14 non-TBI patients had their urine collected every hour for 25 hours, starting 18.3 ± 12.3 days post-injury. We calculated urinary 6-sulfatoxymelatonin concentration to obtain total 24-hour excretion, excretion onset, offset, duration, amplitude, and acrophase. Using Student’s t-tests, we compared groups on actigraphy (daytime activity ratio, nighttime total sleep time, and fragmentation index) and melatonin variables. We investigated associations between melatonin and actigraphy variables using Pearson’s correlations.
Results
TBI patients had poorer daytime activity ratio (TBI: 77.5 ± 9.4%; non-TBI: 84.6 ± 6.9%), shorter nighttime total sleep time (TBI: 353.5 ± 96.6 min; non-TBI: 421.2 ± 72.2 min), and higher fragmentation index (TBI: 72.2 ± 30.0; non-TBI: 53.5 ± 23.6) (all p-values < 0.01). A melatonin rhythm was present in both groups, and no group differences were found on melatonin variables. No associations were found between melatonin and actigraphy variables in TBI patients.
Conclusion
Moderate-to-severe TBI patients have more serious sleep-wake disturbances than non-TBI patients hospitalized in the same environment, suggesting that the brain injury itself alters the sleep-wake cycle. Despite their deregulated 24-hour sleep-wake cycle, TBI patients have a normal circadian clock signal.
Desmoid‐type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm, which occurs in children and adults, with a peak incidence in young adults. For the majority of the patients, DTF is ...a chronic and symptomatic disease, which affects health‐related quality of life. Systemic treatment regimens tend to differ for patients treated by pediatric oncologists compared to medical oncologists. This systematic review identified 14 clinical trials in children and adults with DTF. Tumor response and progression‐free survival rates varied widely between studies and study populations. Treatment choices for patients with DTF are based on a paucity of (randomized) trials. Treatment principles of DTF are similar in pediatric and adult oncology, but the treatment itself is different. This seems mostly driven by a lack of tyrosine kinase inhibitor (TKI) accessibility in pediatric oncology. An insufficient number of studies examined patient‐reported outcomes, which are extremely important for patients with a chronic disease like DTF.
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