Background
Delirium is common in elderly patients after surgery and is associated with poor outcomes. This study aimed to investigate the impact of intraoperative dexmedetomidine on the incidence of ...delirium in elderly patients undergoing major surgery.
Methods
This was a randomized double‐blind placebo‐controlled trial. Elderly patients (aged 60 years or more) scheduled to undergo major non‐cardiac surgery were randomized into two groups. Patients in the intervention group received a loading dose of dexmedetomidine 0·6 μg/kg 10 min before induction of anaesthesia followed by a continuous infusion (0·5 μg per kg per h) until 1 h before the end of surgery. Patients in the control group received volume‐matched normal saline in the same schedule. The primary outcome was the incidence of delirium during the first 5 days after surgery. Delirium was assessed with the Confusion Assessment Method (CAM) for non‐ventilated patients and CAM for the Intensive Care Unit for ventilated patients.
Results
In total, 309 patients who received dexmedetomidine and 310 control patients were included in the intention‐to‐treat analysis. The incidence of delirium within 5 days of surgery was lower with dexmedetomidine treatment: 5·5 per cent (17 of 309) versus 10·3 per cent (32 of 310) in the control group (relative risk (RR) 0·53, 95 per cent c.i. 0·30 to 0·94; P = 0·026). The overall incidence of complications at 30 days was also lower after dexmedetomidine (19·4 per cent (60 of 309) versus 26·1 per cent (81 of 310) for controls; RR 0·74, 0·55 to 0·99, P = 0·047).
Conclusion
Intraoperative dexmedetomidine halved the risk of delirium in the elderly after major non‐cardiac surgery. Registration number: ChiCTR‐IPR‐15007654 (
www.chictr.org.cn).
Antecedentes
El delirio después de la cirugía es frecuente en los pacientes de edad avanzada y se asocia con malos resultados. El objetivo de este estudio fue investigar el impacto de la administración intraoperatoria de dexmedetomidina en la incidencia de delirio en pacientes mayores sometidos a operaciones de cirugía mayor.
Métodos
Se trataba de un ensayo aleatorizado, doble ciego y controlado con placebo. Un total de 620 pacientes mayores (60 años o más) fueron programados para ser sometidos a intervenciones (no cardiacas) de cirugía mayor y se aleatorizaron a dos grupos. Los pacientes en el grupo de intervención recibieron una dosis de carga de dexmedetomidina (0,6 μg/kg, 10 minutos antes de la inducción anestésica) seguida de una infusión continua (0,5 μg/kg/h) hasta 1 h antes de la finalización de la cirugía. Los pacientes del grupo control recibieron el mismo volumen de suero salino siguiendo la misma pauta. El resultado principal era la incidencia de delirio durante los primeros 5 días postoperatorios. Para la valoración del delirio se utilizó el método para la evaluación de la confusión (Confusion Assessment Method, CAM) en pacientes no intubados y el CAM‐UCI para los pacientes intubados.
Resultados
En total, 309 pacientes que recibieron dexmedetomidina y 310 del grupo control se incluyeron en el análisis por intención de tratar. La incidencia de delirio durante los primeros 5 días tras la cirugía fue inferior en presencia de tratamiento con dexmedetomidina que en ausencia del mismo: 5,5% (17/309) versus 10,3% (32/310); riesgo relativo (RR) 0,53, i.c. del 95% 0,30‐0,94, P = 0,026. La incidencia global de complicaciones a los 30 días excluyendo el delirio también fue inferior en presencia que en ausencia de tratamiento con dexmedetomidina (19,4% (60/309) versus 26,1% (81/301), RR 0,74, i.c. del 95% 0,55‐0,99, P = 0,047).
Conclusión
La administración intraoperatoria de dexmedetomidina reduce la presencia de delirio en los pacientes mayores tras cirugía mayor no cardiaca.
In this RCT, intraoperative infusion of dexmedetomidine was found to reduce the rate of postoperative delirium and surgery‐related complications. The shortcomings of previous studies, such as study design and sample size, were amended, providing more robust evidence for clinical practice.
Halved the rate of delirium
A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and ...tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B(1), N-methyl-N'-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3'-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.
Machine learning, a branch of artificial intelligence, learns from previous experience to optimize performance, which is ubiquitous in various fields such as computer sciences, financial analysis, ...robotics, and bioinformatics. A challenge is that machine learning with the rapidly growing "big data" could become intractable for classical computers. Recently, quantum machine learning algorithms Lloyd, Mohseni, and Rebentrost, arXiv.1307.0411 were proposed which could offer an exponential speedup over classical algorithms. Here, we report the first experimental entanglement-based classification of two-, four-, and eight-dimensional vectors to different clusters using a small-scale photonic quantum computer, which are then used to implement supervised and unsupervised machine learning. The results demonstrate the working principle of using quantum computers to manipulate and classify high-dimensional vectors, the core mathematical routine in machine learning. The method can, in principle, be scaled to larger numbers of qubits, and may provide a new route to accelerate machine learning.
Graphene nanosheets (GNs) were synthesized and used as a substitute for platinum as counter-electrode materials for dye-sensitized solar cells (DSSCs). The as-synthesized GNs were dispersed in a ...mixture of terpineol and ethyl cellulose. GN films were screen-printed on fluorine-doped tin oxide (FTO) slides using the formed GN dispersions. GN counter-electrodes were produced by annealing the GN films at different temperatures. The annealed GN films revealed an unusual 3D network structure. Structural and electrochemical properties of the formed GN counter-electrodes were examined by field emission scanning electron microscopy, Raman spectroscopy and electrochemical impedance spectroscopy. It was found that the annealing temperature of GN materials played an important role in the quality of the GN counter-electrode and the photovoltaic performance of the resultant DSSC. The grown DSSCs with graphene-based counter-electrodes exhibited a conversion efficiency high up to 6.81%.
This work aims to present our current best physical understanding of common-envelope evolution (CEE). We highlight areas of consensus and disagreement, and stress ideas which should point the way ...forward for progress in this important but long-standing and largely unconquered problem. Unusually for CEE-related work, we mostly try to avoid relying on results from population synthesis or observations, in order to avoid potentially being misled by previous misunderstandings. As far as possible we debate all the relevant issues starting from physics alone, all the way from the evolution of the binary system immediately before CEE begins to the processes which might occur just after the ejection of the envelope. In particular, we include extensive discussion about the energy sources and sinks operating in CEE, and hence examine the foundations of the standard energy formalism. Special attention is also given to comparing the results of hydrodynamic simulations from different groups and to discussing the potential effect of initial conditions on the differences in the outcomes. We compare current numerical techniques for the problem of CEE and also whether more appropriate tools could and should be produced (including new formulations of computational hydrodynamics, and attempts to include 3D processes within 1D codes). Finally we explore new ways to link CEE with observations. We compare previous simulations of CEE to the recent outburst from V1309 Sco, and discuss to what extent post-common-envelope binaries and nebulae can provide information, e.g. from binary eccentricities, which is not currently being fully exploited.
An epidemic of severe acute respiratory syndrome (SARS) has been associated with an outbreak of atypical pneumonia originating in Guangdong Province, People's Republic of China. We aimed to identify ...the causative agent in the Guangdong outbreak and describe the emergence and spread of the disease within the province.
We analysed epidemiological information and collected serum and nasopharyngeal aspirates from patients with SARS in Guangdong in mid-February, 2003. We did virus isolation, serological tests, and molecular assays to identify the causative agent.
SARS had been circulating in other cities of Guangdong Province for about 2 months before causing a major outbreak in Guangzhou, the province's capital. A novel coronavirus, SARS coronavirus (CoV), was isolated from specimens from three patients with SARS. Viral antigens were also directly detected in nasopharyngeal aspirates from these patients. 48 of 55 (87%) patients had antibodies to SARS CoV in their convalescent sera. Genetic analysis showed that the SARS CoV isolates from Guangzhou shared the same origin with those in other countries, and had a phylogenetic pathway that matched the spread of SARS to the other parts of the world.
SARS CoV is the infectious agent responsible for the epidemic outbreak of SARS in Guangdong. The virus isolated from patients in Guangdong is the prototype of the SARS CoV in other regions and countries.
The choice of general anaesthetics may affect postoperative cognitive outcomes. This study was designed to compare the potential impact of propofol-based vs sevoflurane-based general anaesthesia on ...the development of delayed neurocognitive recovery in older adults early after major cancer surgery.
Older adults (aged ≥65 and <90 yr) who were scheduled to undergo major cancer surgery (≥2 h) were randomised to receive either propofol- or sevoflurane-based general anaesthesia. Cognitive function was assessed before and 1 week after surgery with a battery of neuropsychological tests. Age- and education-matched non-surgical controls were recruited, and their cognitive functions were tested at comparable time intervals in order to adjust for learning effects from repeated tests. Delayed neurocognitive recovery was diagnosed according to the International Study of Postoperative Cognitive Dysfunction 1 definition.
From April 1, 2015 to October 15, 2016, 392 patients were enrolled and randomised. Of these patients, 387 completed the intervention and 30-day follow-up, and 379 completed 1-week neuropsychological tests. Fifty-nine control subjects were enrolled and completed repeated neuropsychological tests. The incidence of delayed neurocognitive recovery at 1 week was significantly lower in the propofol group 14.8% (28/189) than in the sevoflurane group 23.2% (44/190); odds ratio=0.577; 95% confidence interval, 0.342–0.975; P=0.038. Safety outcomes did not differ between the two groups.
When compared with sevoflurane-based general anaesthesia, propofol-based general anaesthesia might decrease the incidence of delayed neurocognitive recovery in older adults after major cancer surgery.
NCT02662257; Chinese Clinical Trial Registry (identifier: ChiCTR-IPR-15006209).
Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy ...(nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC).
Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596).
A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28, with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802).
NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.
•The CMISG1701 trial assessed the safety and efficacy of nCRT versus nCT followed by MIE for locally advanced bulky ESCC.•The nCRT followed by MIE strategy could not improve survival significantly compared with the nCT strategy.•The best strategy of neoadjuvant therapy for locally advanced bulky ESCC remains a pending issue.
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