Enhanced recovery after surgery (ERAS) pathways have not been reported in cardiac surgery. The aim of this study was to evaluate the clinical effectiveness and safety profile of ERAS pathways compared with routine care for patients undergoing cardiac valvular surgery. A randomized clinical trial was conducted between July 2015 and November 2016. A total of 226 patients who underwent elective valvular surgery were randomly assigned to the ERAS pathway or routine care (control) group. The ERAS protocol consisted of an evidence-based systematic optimization approach for managing perioperative patients. The control group received routine care. The primary end-point was readiness for hospital discharge. The secondary outcomes were duration of intensive care unit (ICU) stay, length of postoperative vasoactive drug support, duration of mechanical ventilation, time to first bowel movement, removal of surgical drain, overall medical costs and complication rate. Postoperative time to readiness for discharge was significantly shorter in the ERAS group (6.0 (2.0∼14.0) days) than the control group (7.0 (4.0∼16.0) days, P = 0.01), and the duration of ICU stay and duration of mechanical ventilation were significantly shorter in the ERAS group (20.9 (13.5∼69.3) h, 7.2 (0.0∼22.3) h, respectively) than the control group (22.0 (13.4∼212.3) h, P = 0.001; 8.8 (3.7∼44.9) h, respectively; P < 0.0001). The overall treatment cost of the ERAS group (69202 (52089∼123823) CNY) was significantly lower than that of the control group (77058 (51390∼144290) CNY, P = 0.002). ERAS pathways reduce the length of ICU and hospital stay, postoperative complications and cost for patients undergoing cardiac surgery. ClinicalTrials.gov: NCT02479581.

Sleep disorders increase the risk and mortality of heart disease, but the brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type of cell death activated by the excessive accumulation of intracellular copper. Here, we showed that 16 weeks of sleep fragmentation (SF) resulted in elevated copper levels in the male mouse heart and exacerbated myocardial ischemia–reperfusion injury with increased myocardial cuproptosis and apoptosis. Mechanistically, we found that SF promotes sympathetic overactivity, increases the germination of myocardial sympathetic nerve terminals, and increases the level of norepinephrine in cardiac tissue, thereby inhibits VPS35 expression and leads to impaired ATP7A related copper transport and copper overload in cardiomyocytes. Copper overload further leads to exacerbated cuproptosis and apoptosis, and these effects can be rescued by excision of the sympathetic nerve or administration of copper chelating agent. Our study elucidates one of the molecular mechanisms by which sleep disorders aggravate myocardial injury and suggests possible targets for intervention.

Individuals with diabetes are exposed to a higher risk of perioperative stroke than non-diabetics mainly due to persistent hyperglycemia. LncRNA Meg3 has been considered as an important mediator in regulating ischemic stroke. However, the functional and regulatory roles of Meg3 in diabetic brain ischemic injury remain unclear. In this study, rat brain microvascular endothelial cells (RBMVECs) were exposed to 6 h of oxygen and glucose deprivation (OGD), and subsequent reperfusion via incubating cells with glucose of various high concentrations for 24 h to imitate in vitro diabetic brain ischemic injury. It was shown that the marker events of ferroptosis and increased Meg3 expression occurred after the injury induced by OGD combined with hyperglycemia. However, all ferroptotic events were reversed with the treatment of Meg3-siRNA. Moreover, in this in vitro model, p53 was also characterized as a downstream target of Meg3. Furthermore, p53 knockdown protected RBMVECs against OGD + hyperglycemic reperfusion-induced ferroptosis, while the overexpression of p53 exerted opposite effects, implying that p53 served as a positive regulator of ferroptosis. Additionally, the overexpression or knockdown of p53 significantly modulated GPX4 expression in RBMVECs exposed to the injury induced by OGD combined with hyperglycemic treatment. Furthermore, GPX4 expression was suppressed again after the reintroduction of p53 into cells silenced by Meg3. Finally, chromatin immunoprecipitation assay uncovered that p53 was bound to GPX4 promoter. Altogether, these data revealed that, by modulating GPX4 transcription and expression, the Meg3-p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion.

Hyperventilation is commonly used in neurological patients to decrease elevated intracranial pressure (ICP) or relax a tense brain. However, the potentially deleterious effects of hyperventilation may limit its clinical application. The aim of this review is to summarize the physiological and outcome evidence related to hyperventilation in neurological patients. Physiologically, hyperventilation may adversely decrease cerebral blood flow (CBF) and the match between the cerebral metabolic rate and CBF. In patients with severe traumatic brain injury (TBI), prolonged prophylactic hyperventilation with arterial carbon dioxide tension (PaCO2) less than 25 mmHg or during the first 24 h after injury is not recommended. Most patients (>90%) with an aneurysmal subarachnoid hemorrhage undergo hyperventilation (PaCO2 <35 mmHg); however, whether hyperventilation is associated with poor outcomes in this patient population is controversial. Hyperventilation is effective for brain relaxation during craniotomy; however, this practice is not based on robust outcome evidence. Although hyperventilation is commonly applied in patients with TBI or intracranial hemorrhage or in those undergoing craniotomy, its effects on patient outcomes have not been proven by quality research. Hyperventilation should be used as a temporary measure when treating elevated ICP or to relax a tense brain. Outcome research is needed to better guide the clinical use of hyperventilation in neurological patients. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

Background and Purpose: The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). Methods: We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. Results: Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08–1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10–1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05–1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06–1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28–1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04–1.62]). Conclusions: Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.

This study focuses on seven commonly used hypnotics to comprehensively analyze the effects of long- and short-term use on sleep outcomes among adults and older adults. A network meta-analysis was performed. The insomnia medications were classified into seven categories: benzodiazepines, z-drugs, melatonin, H1-antagonists, orexin receptor antagonists (ORAs), antidepressants, and anticonvulsants. We compared their efficacy of total sleep time, sleep latency, sleep efficiency and wake after sleep onset in subgroups short-term, long-term, elderly, and adults. A total of 111 RCTs involving 25,923 participants were included in this study. ORAs can be widely used in adults and the elderly, and both short-term and long-term use are effective for primary insomnia. H1-antagonists are more effective in adults than in the elderly. Although benzodiazepines have a more obvious effect on sleep maintenance, it is best to reduce their use due to their side effects, especially for the elderly. As a food supplement, melatonin has little effect on adults, but it still has a certain effect on the elderly.