It remains unknown whether there is a causal relationship between intraoperative hypotension and postoperative neurocognitive disorders. We tested the hypothesis that personalised—compared to ...routine—intraoperative blood pressure management reduces the incidence of postoperative neurocognitive disorders in patients having major noncardiac surgery.
In this single-centre trial, 328 elective major noncardiac surgery patients were randomly allocated to receive personalised blood pressure management (i.e. maintaining intraoperative mean arterial pressure MAP above preoperative baseline MAP from automated 24-h blood pressure monitoring) or routine blood pressure management (i.e. maintaining MAP above 65 mm Hg). The primary outcome was the incidence of neurocognitive disorders (composite of delayed neurocognitive recovery and delirium) between postoperative days 3 and 7.
The primary outcome, neurocognitive disorders, occurred in 18 of 147 patients (12%) assigned to personalised and 21 of 148 patients (14%) assigned to routine blood pressure management (odds ratio OR=0.84, 95% confidence interval CI: 0.40–1.75, P=0.622). Delayed neurocognitive recovery occurred in 17 of 146 patients (12%) assigned to personalised and 17 of 145 patients (12%) assigned to routine blood pressure management (OR=0.99, 95% CI: 0.45–2.17, P=0.983). Delirium occurred in 2 of 157 patients (1%) assigned to personalised and 4 of 158 patients (3%) assigned to routine blood pressure management (OR=0.50, 95% CI: 0.04–3.53, P=0.684).
Personalised intraoperative blood pressure management maintaining preoperative baseline MAP neither reduced the incidence of the composite primary outcome neurocognitive disorders between postoperative days 3 and 7 nor the incidences of the components of the composite primary outcome—delayed neurocognitive recovery and delirium—compared to routine blood pressure management in patients having major noncardiac surgery.
ClinicalTrials.gov (NCT03442907).
Background: This study aimed to determine whether prehospital qSOFA (quick sequential organ failure assessment) assessment was associated with a shortened ‘time to antibiotics’ and ‘time to ...intravenous fluid resuscitation’ compared with standard assessment. Methods: This retrospective study included patients who were referred to our Emergency Department between 2014 and 2018 by emergency medical services, in whom sepsis was diagnosed during hospitalization. Two multivariable regression models were fitted, with and without qSOFA parameters, for ‘time to antibiotics’ (primary endpoint) and ‘time to intravenous fluid resuscitation’. Results: In total, 702 patients were included. Multiple linear regression analysis showed that antibiotics and intravenous fluids were initiated earlier if infections were suspected and emergency medical services involved emergency physicians. A heart rate above 90/min was associated with a shortened time to antibiotics. If qSOFA parameters were added to the models, a respiratory rate ≥ 22/min and altered mentation were independent predictors for earlier antibiotics. A systolic blood pressure ≤ 100 mmHg and altered mentation were independent predictors for earlier fluids. When qSOFA parameters were added, the explained variability of the model increased by 24% and 38%, respectively (adjusted R² 0.106 versus 0.131 for antibiotics and 0.117 versus 0.162 for fluids). Conclusion: Prehospital assessment of qSOFA parameters was associated with a shortened time to a targeted sepsis therapy.
•The theoretical background of FRET and single-molecule TIRF microscopy,•Considerations to prepare proteins of interest for donor/acceptor labeling and surface immobilization.•The procedures ...involved, as well as the principles of data analysis:•Image analysis and the determination of FRET time traces.•The extraction of rate constants from FRET time traces.•The general conclusions that can be drawn from these data.•A case study to illustrate individual aspects of experimental design, data analysis, and the interpretation in the biological context.
RNA helicases couple nucleotide-driven conformational changes to the unwinding of RNA duplexes. Interaction partners can regulate helicase activity by altering the rate constants of these conformational changes. Single-molecule FRET experiments on donor/acceptor-labeled, immobilized molecules are ideally suited to monitor conformational changes in real time and to extract rate constants for these processes. This article provides guidance on how to design, perform, and analyze single-molecule FRET experiments by TIRF microscopy. It covers the theoretical background of FRET and single-molecule TIRF microscopy, the considerations to prepare proteins of interest for donor/acceptor labeling and surface immobilization, and the principles and procedures of data analysis, including image analysis and the determination of FRET time traces, the extraction of rate constants from FRET time traces, and the general conclusions that can be drawn from these data. A case study, using the DEAD-box protein eIF4A as an example, highlights how single-molecule FRET studies have been instrumental in understanding the role of conformational changes for duplex unwinding and for the regulation of helicase activities. Selected examples illustrate which conclusions can be drawn from the kinetic data obtained, highlight possible pitfalls in data analysis and interpretation, and outline how kinetic models can be related to functionally relevant states.
What has happened to cities after the global economic recession?Sustaining Citiesanswers this question by explaining how failed governmental policies contributed to urban problems and offering best ...practices for solving them.
From social scientists and urban planners to architects and literary and film critics, the authors of this unique collection suggest real responses to this crisis. Could the drastic declines in housing markets have been avoided? Yes, if we reframe our housing values. Do you want to attract corporate investment to your town? You might want to think twice about doing so. The extinction of the "Celtic Tiger" may be charted in statistics, but the response in popular Irish mystery novels is much more compelling. China, while not immune to market vicissitudes, still booms, but at a considerable cost to its urban identities.
Whether constructing a sustainable social framework for Mexican mega-cities or a neighborhood in London, these nine essays consider some strikingly similar strategies. And perhaps, as the contributors suggest, it's time to look beyond the usual boundaries of urban, suburban, and exurban to forge new links among these communities that will benefit all citizens. Accessible to anyone with an interest in how cities cope today,Sustaining Citiespresents a cautionary tale with a hopeful ending.
Translation initiation in eukaryotes starts with the recognition of the mRNA 5'-cap by eIF4F, a hetero-trimeric complex of eIF4E, the cap-binding protein, eIF4A, a DEAD-box helicase, and eIF4G, a ...scaffold protein. eIF4G comprises eIF4E- and eIF4A-binding domains (4E-BD, 4A-BD) and three RNA-binding regions (RNA1-RNA3), and interacts with eIF4A, eIF4E, and with the mRNA. Within the eIF4F complex, the helicase activity of eIF4A is increased. We showed previously that RNA3 of eIF4G is important for the stimulation of the eIF4A conformational cycle and its ATPase and helicase activities. Here, we dissect the interplay between the eIF4G domains and the role of the eIF4E/cap interaction in eIF4A activation. We show that RNA2 leads to an increase in the fraction of eIF4A in the closed state, an increased RNA affinity, and faster RNA unwinding. This stimulatory effect is partially reduced when the 4E-BD is present. eIF4E binding to the 4E-BD then further inhibits the helicase activity and closing of eIF4A, but does not affect the RNA-stimulated ATPase activity of eIF4A. The 5'-cap renders the functional interaction of mRNA with eIF4A less efficient. Overall, the activity of eIF4A at the 5'-cap is thus fine-tuned by a delicately balanced network of stimulatory and inhibitory interactions.
The universal bed model for patient care improves outcome and lowers cost in cardiac surgery Emaminia, Abbas, MD; Corcoran, Phillip C., MD; Siegenthaler, Michael P., MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
02/2012, Letnik:
143, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Objective With the escalating demands to increase the efficiency and decrease the cost, innovations in postoperative cardiac surgical patient care are needed. The universal bed model is an innovative ...care delivery system that allows patient care to be managed in one setting from postoperation to discharge. We hypothesized that the universal bed model in the context of cardiac surgery would improve outcomes and efficacy. Methods A total of 610 consecutive patients were admitted to the universal bed unit and prospectively entered into the Society of Thoracic Surgeons National Cardiac Database. Intensive care unit level of care was determined by acuity and staffing needs. Telemetry was employed from admission to discharge, and multidisciplinary rounds were conducted twice daily. Postoperative outcomes were recorded during hospital stay, and comparisons were made with the Society of Thoracic Surgeons National Cardiac Database using identical variables over the same period of time. Results Decreased ventilation time, intensive care unit and hospital stay, and reduction in the incidence of atrial fibrillation and infectious complications yielded a financial benefit in the universal bed group compared with the traditional model of admission. Stroke rate and in-hospital mortality were the same compared with regional and national centers. Compared with regional centers, there was an average cost savings between $6200 and $9500 per patient depending on the operation. Patient care satisfaction by independent survey was in the 99th percentile. Conclusions The universal bed patient care model allows for expedient and efficacious care as measured by decreased length of intensive care unit and hospital stay, improved postoperative outcomes, patient satisfaction, and cost savings.
Perioperative hemodynamic management aims to optimize organ perfusion pressure and blood flow-assuming this ensures that oxygen delivery meets cellular metabolic needs. Cellular metabolic needs are ...reflected by energy expenditure. A better understanding of energy expenditure under general anesthesia could help tailor perioperative hemodynamic management to actual demands. We thus sought to assess energy expenditure under general anesthesia. Our primary hypothesis was that energy expenditure under general anesthesia is lower than preoperative awake resting energy expenditure.
We conducted an observational study on patients having elective noncardiac surgery at the University Medical Center Hamburg-Eppendorf (Germany) between September 2019 and March 2020. We assessed preoperative awake resting energy expenditure, energy expenditure under general anesthesia, and energy expenditure after surgery using indirect calorimetry. We compared energy expenditure under general anesthesia at incision to preoperative awake resting energy expenditure using a Wilcoxon signed-rank test for paired measurements.
We analyzed 60 patients. Median (95% confidence interval CI) preoperative awake resting energy expenditure was 953 (95% CI, 906-962) kcal d -1 m -2 . Median energy expenditure under general anesthesia was 680 (95% CI, 642-711) kcal d -1 m -2 -and thus 263 (95% CI, 223-307) kcal d -1 m -2 or 27% (95% CI, 23%-30%) lower than preoperative awake resting energy expenditure ( P < .001).
Median energy expenditure under general anesthesia is about one-quarter lower than preoperative awake resting energy expenditure in patients having noncardiac surgery.
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