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1.

Objectives

Expedient extubation after cardiac surgery has been associated with improved outcomes, leading to postoperative extubation frequently during overnight hours. However, recent evidence in a mixed medical-surgical intensive care unit population demonstrated worse outcomes with overnight extubation. This study investigated the impact of overnight extubation in a statewide, multicenter Society of Thoracic Surgeons database.

Methods

Records from 39,812 patients undergoing coronary artery bypass grafting or valve operations (2008-2016) and extubated within 24 hours were stratified according to extubation time between 06:00 and 18:00 (day) or between 18:00 and 6:00 (overnight). Outcomes including reintubation, mortality, and composite morbidity-mortality were evaluated using hierarchical regression models adjusted for Society of Thoracic Surgeons predictive risk scores. To further analyze extubation during the night, a subanalysis stratified patients into 3 groups: 06:00 to 18:00, 18:00 to 24:00, and 24:00 to 06:00.

Results

A total of 20,758 patients were extubated overnight (52.1%) and were slightly older (median age 66 vs 65 years, P < .001) with a longer duration of ventilation (4 vs 7 hours, P < .001). Day and overnight extubation were associated with equivalent operative mortality (1.7% vs 1.7%, P = .880), reintubation (3.7% vs 3.4%, P = .141), and composite morbidity-mortality (8.2% vs 8.0%, P = .314). After risk adjustment, overnight extubation was not associated with any difference in reintubation, mortality, or composite morbidity-mortality. On subanalysis, those extubated between 24:00 and 06:00 exhibited increased composite morbidity-mortality (odds ratio, 1.18; P = .001) but no difference in reintubation or mortality.

Conclusions

Extubation overnight was not associated with increased mortality or reintubation. These results suggest that in the appropriate clinical setting, it is safe to routinely extubate cardiac surgery patients overnight.  相似文献   
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Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs.  相似文献   
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Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.  相似文献   
9.
Objectives: The steeling effect suggests that early-life adversity can have a beneficial impact later in life. However, little is known about its underlying mechanisms and long-term outcomes . The study aimed to examine the role of early-life adversity (ELA) on successful aging, and whether this relationship can be explained by mental and physical health.

Method: Socio-demographics, early-life adversity (ELA), individual quality of life (iQoL), and mental and physical health of 270 individuals (Mage = 66.82 years, 71.5% female) were assessed. Polynomial regressions and mediation analyses were conducted.

Results: Significant inverse U-shaped associations were found between ELA and iQoL (β = ?.59, p = .005) and between ELA and mental health (β = ?.64, p = .002), but not between ELA and physical health. Furthermore, mental health significantly mediated the relationship between ELA and iQoL (b = ?.84, BCa CI [?1.66, ?.27]).

Conclusion: Highest level of individual quality of life (i.e. successful aging) was related to a moderate amount of ELA. Additionally, mental health significantly mediated this relationship. These findings suggest that some amount of ELA could be beneficial for successful aging. Resource-focused interventions are needed to improve health and promote successful aging for an underdetected, at-risk subgroup with low early-life adversity.  相似文献   

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BACKGROUND AND PURPOSE:In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase.MATERIALS AND METHODS:Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MDz). Through linear regression, we evaluated the relation between microbleed concentration and MDz in predefined structures.RESULTS:In the cerebral hemispheres, MDz at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5–69.3], P = .017; right: B = 26.3 [95% CI 5.7–47.0], P = .014). No such relation was demonstrated in the central brain. MDz in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8–75.2], P < .000). MDz in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9–47.5], P = .023).CONCLUSIONS:SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

The yearly incidence of traumatic brain injury (TBI) is around 300 per 100,000 persons.1,2 Almost three-quarters of patients with moderate to severe TBI have traumatic axonal injury (TAI).3 TAI is a major predictor of functional outcome,4,5 but it is mostly invisible on CT and conventional MR imaging.6,7DTI provides direct information on WM integrity and axonal injury.5,8 However, DTI abnormalities are neither specific for TAI nor stable over time. Possibly because of the release of mass effect and edema and resorption of blood products, the effects of concomitant (non-TAI) injury on DTI are larger in the subacute than in the chronic phase (>3 months).4,9,10 Therefore, DTI findings are expected to reflect TAI more specifically in the chronic than in the subacute phase (1 week–3 months).4 Even in regions without concomitant injury, the effects of TAI on DTI are dynamic, possibly caused by degeneration and neuroplastic changes.6,11,12 These ongoing pathophysiological processes possibly contribute to the emerging evidence that DTI findings in the chronic phase are most closely associated with the eventual functional outcome.12,13Although DTI provides valuable information, its acquisition, postprocessing, and interpretation in individual patients are demanding. SWI, with which microbleeds can be assessed with high sensitivity, is easier to interpret and implement in clinical practice. In contrast to DTI, SWI-detected traumatic microbleeds are more stable1 except in the hyperacute14,15 and the late chronic phases.16 Traumatic cerebral microbleeds are commonly interpreted as signs of TAI. However, the relation is not straightforward. On the one hand, nontraumatic microbleeds may be pre-existing. On the other hand, even if traumatic in origin, microbleeds represent traumatic vascular rather than axonal injury.17 Indeed, TAI is not invariably hemorrhagic.18 Additionally, microbleeds may secondarily develop after trauma through mechanisms unrelated to axonal injury, such as secondary ischemia.18DTI is not only affected by pathophysiological changes but also by susceptibility.19 The important susceptibility-effect generated by microbleeds renders the interpretation of DTI findings at the location of microbleeds complex. In the chronic phase, mean diffusivity (MD) is the most robust marker of WM integrity.4,6 For these reasons, we evaluated MD in the normal-appearing WM.Much TAI research focuses on the corpus callosum because it is commonly involved in TAI5,18,20 and it can reliably be evaluated with DTI,5,21 and TAI in the corpus callosum is related to clinical prognosis.6,20 The corpus callosum consists of densely packed WM tracts that structurally and functionally connect left- and right-sided brain structures.22 The integrity of the corpus callosum is associated with the integrity of the brain structures it connects.23 Therefore, microbleeds in brain structures that are connected through the corpus callosum may affect callosal DTI findings. Analogous to this, microbleeds in the cerebral hemispheres, which exert their function through WM tracts traveling through the deep brain structures and brain stem,24,25 may affect DTI findings in the WM of the latter.Our purpose was to evaluate whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. We investigated this relation within the cerebral hemispheres and the central brain and between regions that are functionally connected by WM tracts.  相似文献   
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