Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the ...incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.
We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.
CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.
CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.
Preliminary to successful assembling, drilling of composites like carbon-fiber reinforced polymers (CFRP) is an important but difficult process. The anisotropic and heterogeneous structure of the ...laminates and the highly abrasive nature of the carbon fibers make it prone to critical damages in the workpiece as well as extensive tool wear. In this work, drill series with uncoated and diamond coated tungsten carbide hard metal tools were performed in two CFRP laminates with significant differences in their microstructure. The tool wear behavior and the corresponding workpiece damage were intensively studied to figure out the correlations between wear and delamination damage. Therefore, novel and well established methods in tool wear analysis and delamination assessment based on light optical microscopy were applied and critically evaluated.
The abrasive tool wear on uncoated carbide drill can be well described by the cutting edge rounding (CER) allowing strong correlations with the inflicted workpiece damage, whereas for coated tools measuring CER is not an appropriate method. The machinability of CFRP was found to be highly influenced by the presence of residual porosity in the composite laminate. Hence, the benefit in lifetime of the diamond coating can only be utilized in machining of high quality laminates.
The time-dependent decrease of the magnetic polarization of magnet materials in the presence of an opposing field is well known as the magnetic viscosity or magnetic aftereffect. In previous studies, ...magnetic viscosity was usually measured in fields when in the vicinity of coercivity HcJ, and this was conducted in order to understand the coercivity mechanism in magnetic materials. In this study, the magnetic viscosity of commercial FeNdB magnets is determined at opposing fields weaker than HcJ and at different temperatures in the range from 303 to 433 K (i.e., from 30 to 160 °C) by means of a vibrating sample magnetometer (VSM). As a result, the parameter Sv, which describes the magnetic viscosity in the material, was found to increase with increases in the opposing field. Furthermore, both the parameter Sv and its dependence on the temperature were found to correlate with the coercivity HcJ of the material. Also, a difference with regard to the parameter Sv for the materials measured in this study with similar magnetic properties, but which had undergone different types of processing, could not be found. Knowledge of the field- and temperature-dependent behavior of the magnetic viscosity of FeNdB magnets allows for better estimations over the lifetime of a component under operating conditions with respect to the magnetic losses in FeNdB magnets that are used in electric components.
Preexisting factors such as age and cognitive performance can influence the electroencephalogram (EEG) during general anesthesia. Specifically, spectral EEG power is lower in elderly, compared to ...younger, subjects. Here, the authors investigate age-related changes in EEG architecture in patients undergoing general anesthesia through a detailed examination of spectral and entropic measures.
The authors retrospectively studied 180 frontal EEG recordings from patients undergoing general anesthesia, induced with propofol/fentanyl and maintained by sevoflurane at the Waikato Hospital in Hamilton, New Zealand. The authors calculated power spectral density and normalized power spectral density, the entropic measures approximate and permutation entropy, as well as the beta ratio and spectral entropy as exemplary parameters used in current monitoring systems from segments of EEG obtained before the onset of surgery (i.e., with no noxious stimulation).
The oldest quartile of patients had significantly lower 1/f characteristics (P < 0.001; area under the receiver operating characteristics curve, 0.84 0.76 0.92), indicative of a more uniform distribution of spectral power. Analysis of the normalized power spectral density revealed no significant impact of age on relative alpha (P = 0.693; area under the receiver operating characteristics curve, 0.52 0.41 0.63) and a significant but weak effect on relative beta power (P = 0.041; area under the receiver operating characteristics curve, 0.62 0.52 0.73). Using entropic parameters, the authors found a significant age-related change toward a more irregular and unpredictable EEG (permutation entropy: P < 0.001, area under the receiver operating characteristics curve, 0.81 0.71 0.90; approximate entropy: P < 0.001; area under the receiver operating characteristics curve, 0.76 0.66 0.85). With approximate entropy, the authors could also detect an age-induced change in alpha-band activity (P = 0.002; area under the receiver operating characteristics curve, 0.69 0.60 78).
Like the sleep literature, spectral and entropic EEG features under general anesthesia change with age revealing a shift toward a faster, more irregular, oscillatory composition of the EEG in older patients. Age-related changes in neurophysiological activity may underlie these findings however the contribution of age-related changes in filtering properties or the signal to noise ratio must also be considered. Regardless, most current EEG technology used to guide anesthetic management focus on spectral features, and improvements to these devices might involve integration of entropic features of the raw EEG.
Abstract Isoflurane anesthesia (IA) partially compensates NREM sleep (NREMS) and not REM sleep (REMS) requirement, eliciting post-anesthetic REMS rebound. Sleep deprivation triggers compensatory ...NREMS rebounds and REMS rebounds during recovery sleep as a result of the body’s homeostatic mechanisms. A combination of sleep deprivation and isoflurane anesthesia is common in clinical settings, especially prior to surgeries. This study investigates the effects of pre-anesthetic sleep deprivation on post-anesthetic sleep–wake architecture. The effects of isoflurane exposure (90 min) alone were compared with the effects of isoflurane exposure preceded by experimental sleep deprivation (6 h, gentle handling) on recovery sleep in adult mice by studying the architecture of post-anesthetic sleep for 3 consecutive post-anesthetic days. Effects of isoflurane anesthesia on recovery sleep developed only during the first dark period after anesthesia, the active phase in mice. During this time, mice irrespective of preceding sleep pressure, showed NREMS and REMS rebound and decreased wakefulness during recovery sleep. Additionally, sleep deprivation prior to isoflurane treatment caused a persistent reduction of theta power during post-anesthetic REMS at least for 3 post-anesthetic days. We showed that isoflurane causes NREMS rebound during recovery sleep which suggests that isoflurane may not fully compensate for natural NREMS. The study also reveals that isoflurane exposure preceded by sleep deprivation caused a persistent disruption of REMS quality. We suggest that preoperative sleep deprivation may impair postoperative recovery through lasting disruption in sleep quality.
Background
Australian hospital data on hyperglycaemia without previously known diabetes are lacking.
Aims
To determine the prevalence of hyperglycaemia without previously recognised diabetes among ...all patients screened in the emergency department (ED). Secondary aims are to describe the extent of haemoglobin A1c testing for evaluation of new diabetes, adequate glucose monitoring, treatment of significant hyperglycaemia and documented follow‐up plans.
Methods
Patients presenting to ED at the Alfred (tertiary hospital in Melbourne) have undergone screening random plasma glucose (RPG) with their first plasma biochemistry since 2015. Of the 16 268 adults screened from July to December 2015, a retrospective, cross‐sectional study was undertaken evaluating those with hyperglycaemia (RPG >7.8 mmol/L) but without previously recognised diabetes as determined from coding data. After patient records were reviewed to correct for coding errors, a nested cohort of 200 such patients were further evaluated. Glucose monitoring was deemed adequate if undertaken for ≥48 h. Significant hyperglycaemia (RPG >11 mmol/L) was considered appropriately treated if insulin/hypoglycaemic agents were prescribed. Documented follow‐up plans were acceptable if found in the discharge summary.
Results
Among all patients screened, 1178 had hyperglycaemia without coded diabetes. After adjusting for coding errors, the prevalence was 5.2%. Within the nested cohort, only 7.5% had a follow‐up haemoglobin A1c ordered, 9.5% underwent adequate glucose monitoring, 6.5% had appropriate treatment of significant hyperglycaemia and 2% had documentation of a follow‐up plan.
Conclusions
Hyperglycaemia without previously recognised diabetes is commonly seen and justifies ED screening. However, management of newly detected hyperglycaemia in these patients is suboptimal and requires improvement.
Excessive workload may impair patient safety. However, little is known about emergency care providers' workload during the treatment of life-threatening cases including cardiopulmonary resuscitation ...(CPR). Therefore, we tested the hypothesis that subjective and physiological indicators of workload are associated with the patient's initial NACA score and that workload is particularly high during CPR.
NASA task load index (NASA-tlx) and alarm codes were obtained for 216 sorties of pre-hospital emergency medical care. Furthermore, initial NACA scores of 140 patients were extracted from the physicians' protocols. The physiological workload indicators mean heart rate (HR) and permutation entropy (PeEn) were calculated for 51 sorties of primary care. General linear mixed models were used to analyze the association of NACA scores with subjective (NASA-tlx) and physiological (mean HR, PeEn) measures of workload.
In contrast to the physiological variables PeEn (p = 0.10) and HR (p = 0.19), the mental (p<0.001) and temporal demands (p<0.001) as well as the effort (p<0.001) and frustration (p = 0.04) subscale of the NASA-tlx were significantly associated with initial NACA scores. Compared to NACA = I, an initial NACA score of VI (representing CPR) increased workload by a mean of 389.5% (p = 0.001) in the mental and 345.9% (p<0.001) in the temporal demands, effort by a mean of 446,8% (p = 0.002) and frustration by 190.0% (p = 0.03). In line with the increase in NASA-tlx, PeEn increased by 20.6% (p = 0.01) and HR by 6.4% (p = 0.57).
Patients' initial NACA scores are associated with subjective workload. Workload was highest during CPR.
Previous studies have shown that xenon reduces hyperpolarization-activated cyclic nucleotide-gated channels type-2 (HCN2) channel-mediated current (I
) amplitude and shifts the half-maximal ...activation voltage (V1/2) in thalamocortical circuits of acute brain slices to more hyperpolarized potentials. HCN2 channels are dually gated by the membrane voltage and via cyclic nucleotides binding to the cyclic nucleotide-binding domain (CNBD) on the channel. In this study, we hypothesize that xenon interferes with the HCN2 CNBD to mediate its effect. Using the transgenic mice model HCN2EA, in which the binding of cAMP to HCN2 was abolished by two amino acid mutations (R591E, T592A), we performed ex-vivo patch-clamp recordings and in-vivo open-field test to prove this hypothesis. Our data showed that xenon (1.9 mM) application to brain slices shifts the V1/2 of I
to more hyperpolarized potentials in wild-type thalamocortical neurons (TC) (V1/2: -97.09 -99.56--95.04 mV compared to control -85.67 -94.47--82.10 mV;
= 0.0005). These effects were abolished in HCN2EA neurons (TC), whereby the V1/2 reached only -92.56 -93.16- -89.68 mV with xenon compared to -90.03 -98.99--84.59 mV in the control (
= 0.84). After application of a xenon mixture (70% xenon, 30% O
), wild-type mice activity in the open-field test decreased to 5 2-10 while in HCN2EA mice it remained at 30 15-42%, (
= 0.0006). In conclusion, we show that xenon impairs HCN2 channel function by interfering with the HCN2 CNBD site and provide in-vivo evidence that this mechanism contributes to xenon-mediated hypnotic properties.
A key feature of the human brain is its capability to adapt flexibly to changing external stimuli. This capability can be eliminated by general anesthesia, a state characterized by unresponsiveness, ...amnesia, and (most likely) unconsciousness. Previous studies demonstrated decreased connectivity within the thalamus, frontoparietal, and default mode networks during general anesthesia. We hypothesized that these alterations within specific brain networks lead to a change of communication between networks and their temporal dynamics.
We conducted a pooled spatial independent component analysis of resting-state functional magnetic resonance imaging data obtained from 16 volunteers during propofol and 14 volunteers during sevoflurane general anesthesia that have been previously published. Similar to previous studies, mean z-scores of the resulting spatial maps served as a measure of the activity within a network. Additionally, correlations of associated time courses served as a measure of the connectivity between networks. To analyze the temporal dynamics of between-network connectivity, we computed the correlation matrices during sliding windows of 1 min and applied k-means clustering to the matrices during both general anesthesia and wakefulness.
Within-network activity was decreased in the default mode, attentional, and salience networks during general anesthesia (P < 0.001, range of median changes: -0.34, -0.13). Average between-network connectivity was reduced during general anesthesia (P < 0.001, median change: -0.031). Distinct between-network connectivity patterns for both wakefulness and general anesthesia were observed irrespective of the anesthetic agent (P < 0.001), and there were fewer transitions in between-network connectivity patterns during general anesthesia (P < 0.001, median number of transitions during wakefulness: 4 and during general anesthesia: 0).
These results suggest that (1) higher-order brain regions play a crucial role in the generation of specific between-network connectivity patterns and their dynamics, and (2) the capability to interact with external stimuli is represented by complex between-network connectivity patterns.
Dexmedetomidine is a selective α
-adrenoceptor agonist and appears to disinhibit endogenous sleep-promoting pathways, as well as to attenuate noradrenergic excitation. Recent evidence suggests that ...dexmedetomidine might also directly inhibit hyperpolarization-activated cyclic-nucleotide gated (HCN) channels. We analyzed the effects of dexmedetomidine on native HCN channel function in thalamocortical relay neurons of the ventrobasal complex of the thalamus from mice, performing whole-cell patch-clamp recordings. Over a clinically relevant range of concentrations (1-10 µM), the effects of dexmedetomidine were modest. At a concentration of 10 µM, dexmedetomidine significantly reduced maximal I
amplitude (relative reduction: 0.86 0.78-0.91, n = 10, and
= 0.021), yet changes to the half-maximal activation potential V
occurred exclusively in the presence of the very high concentration of 100 µM (-4,7 -7.5--4.0 mV, n = 10, and
= 0.009). Coincidentally, only the very high concentration of 100 µM induced a significant deceleration of the fast component of the HCN activation time course (τ
: +135.1 +64.7-+151.3 ms, n = 10, and
= 0.002). With the exception of significantly increasing the membrane input resistance (starting at 10 µM), dexmedetomidine did not affect biophysical membrane properties and HCN channel-mediated parameters of neuronal excitability. Hence, the sedative qualities of dexmedetomidine and its effect on the thalamocortical network are not decisively shaped by direct inhibition of HCN channel function.